Ruben Alvero, M.D.

All Publications

• A Cost Analysis of Clomiphene Citrate, Letrozole and Gonadotropin with Intrauterine Insemination using Outcome Data from the AMIGOS Trial. Fertility and sterility Cardozo, E. R., Alvero, R., Diamond, M. P., Santoro, N., Bavan, B. 2024

  View details for DOI 10.1016/j.fertnstert.2024.10.032

  View details for PubMedID 39447828

• LGBTQ+ Family Building: Progress but Lots More to Do. Fertility and sterility Alvero, R. 2024

  Abstract

  Great strides have been made in society and in Reproductive Endocrinology and Infertility (REI) in support of LGBTQ+ family building. While many of the concepts used in heterosexual reproduction can be applied to the LGBTQ+ community, there are specific differences that must be understood to provide the highest level of care to this community.

  View details for DOI 10.1016/j.fertnstert.2024.09.027

  View details for PubMedID 39303898

• Climate change and human health: a primer on what women's health physicians can do on behalf of their patients and communities. Current opinion in obstetrics & gynecology Alvero, R. 2024; 36 (4): 228-233

  Abstract

  To describe the current state of knowledge on the impact on climate change on women's health and to highlight opportunities for healthcare providers to serve as advocates and subject matter experts.Healthcare providers are a uniquely respected voice in society but have not used this advantage to advocate for their communities and participate in mitigation, adaptation, and resiliency efforts on behalf of their patients and communities.Healthcare providers feel that climate change is real, is human caused, and is currently or will shortly negatively impact their patients. They feel unprepared to serve as leaders and advocates due to time limitations and a knowledge gap. Resources in the current climate movement can help close this gap.

  View details for DOI 10.1097/GCO.0000000000000958

  View details for PubMedID 38934104

• Reproductive endocrinology and infertility in 2024: promise and turmoil. Current opinion in obstetrics & gynecology Alvero, R. 2024; 36 (4): 209-210

  View details for DOI 10.1097/GCO.0000000000000964

  View details for PubMedID 38934103

• Initial fertility evaluation with saline sonography vs. hysterosalpingography: it is debate-tubal. Fertility and sterility Nguyen, E., Strug, M., Gardner, A., Burney, R., Campbell, S., Aghajanova, L. 2024

  View details for DOI 10.1016/j.fertnstert.2024.04.003

  View details for PubMedID 38703168

• Anatomic fertility assessment: everything old is new again. Fertility and sterility Alvero, R. 2024

  View details for DOI 10.1016/j.fertnstert.2024.04.001

  View details for PubMedID 38703169

• Concordance of hemoglobin A1c and reproductive hormone levels in menstrual and venous blood. F&S reports Naseri, S., Avrutsky, M. I., Capati, C., Desai, K., Alvero, R., Blumenthal, P. D. 2024; 5 (1): 33-39

  Abstract

  To explore whether menstrual blood collected via a modified menstrual pad is a surrogate for venous blood drawn in analyzing hemoglobin A1c (HbA1c) and fertility-associated hormones.Cross-sectional study.Clinical testing laboratory.This study included 152 female participants who have regular menses, aged 19-50 years old.Participants collected menstrual effluent using a menstrual pad modified with a removable dried blood spot (DBS) strip. Peripheral blood samples were collected via venipuncture within 60 hours of menstrual pad use.Menstrual pad and venous blood drawn samples were analyzed for levels of HbA1c, thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH), anti-müllerian hormone (AMH), and luteinizing hormone (LH). Correlation between menstrual pad and venipuncture samples was performed using Deming linear regression, and r coefficients were measured using Pearson correlation.The interassay variability of menstrual pad DBS sample measurements was <6%. Menstrual HbA1c values were stabilized in the DBS strips through 53 days, and menstrual hormone levels remained stable through 15 days. Menstrual HbA1c levels were highly correlated with venipuncture samples (r = 0.96). The levels of TSH (r = 0.94), AMH (r = 0.94), FSH (r = 0.91), and LH (r = 0.91) also showed a high correlation between menstrual strip and venipuncture samples.The levels of HbA1c, TSH, AMH, FSH, and LH measurements in menstrual effluent showed a high correlation to venous blood samples, supporting the use of menstrual effluent as a surrogate sample for hormone testing.

  View details for DOI 10.1016/j.xfre.2023.11.009

  View details for PubMedID 38524214

  View details for PubMedCentralID PMC10958681

• Closing the Gap on Racial Disparities - Increasing Race/Ethnicity Demographics Reporting in the SART CORS Registry. Fertility and sterility Seifer, D. B., Richard-Davis, G., Alvero, R. 2024

  View details for DOI 10.1016/j.fertnstert.2024.02.012

  View details for PubMedID 38346548

• Utility of Repeat Uterine Cavity Evaluation in the Infertility Workup. Journal of women's health (2002) Dolinko, A. V., Danilack, V. A., Alvero, R. J., Snegovskikh, V. V. 2023

  Abstract

  Background: Uterine cavity abnormalities contribute to infertility. The purpose of this study was to evaluate the incidence, recurrence rates, and risk factors for uterine cavity abnormalities in women undergoing infertility workup and treatment, focusing on the utility of routinely repeated imaging. Methods: Retrospective cohort study at single academic medical center of 833 infertile women who had uterine cavity evaluations performed at least 9 months apart. Results: Of 833 eligible patients, 664 (79.7%) had normal initial imaging and 169 (20.3%) had abnormal initial imaging. Among the former, 10% had abnormal uterine cavity on repeat saline infusion sonohysterography (SIS); among the latter, 32% had abnormal repeat SIS [Chi-square p < 0.0001, risk ratio 2.30 (95% confidence interval 1.85-2.86)]. On average, 23.1 ± 13.6 months passed between studies. Regardless of initial imaging findings, women with abnormal repeat SIS were older than those with normal repeat SIS, with no difference in time elapsed between studies. There were no associations between repeat imaging outcomes and body mass index, uterine instrumentation, number of treatment cycles, or maximum peak estradiol levels in a single cycle between studies. There was no difference in live birth rate among cycles started within 1 year after repeat SIS across groups. Conclusions: Uterine cavity abnormalities were found in 10% of patients on repeat imaging despite initially normal testing. No risk factors for cavity abnormality on repeat imaging were identified besides age and prior abnormality. It would be prudent to continue performing routine repeat uterine cavity evaluation for women undergoing fertility treatment, particularly if corrective measures had been taken in the past.

  View details for DOI 10.1089/jwh.2023.0302

  View details for PubMedID 38117546

• HOW SHOULD WE MEET THE INCREASING NEED FOR FERTILITY SERVICES? Clain, E., Hill, M. J., Alvero, R. J., Shannon, C. N., Devine, K. ELSEVIER SCIENCE INC. 2023: E31

  View details for Web of Science ID 001084670200074

• Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States. Fertility and sterility Hariton, E., Alvero, R., Hill, M. J., Mersereau, J. E., Perman, S., Sable, D., Wang, F., Adamson, G. D., Coutifaris, C., Craig, L. B., Hosseinzadeh, P., Imudia, A. N., Johnstone, E. B., Lathi, R. B., Lin, P. C., Marsh, E. E., Munch, M., Richard-Davis, G., Roth, L. W., Schutt, A. K., Thornton, K., Verrilli, L., Weinerman, R. S., Young, S. L., Devine, K. 2023

  Abstract

  The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

  View details for DOI 10.1016/j.fertnstert.2023.08.019

  View details for PubMedID 37665313

• Editorial introductions CURRENT OPINION IN OBSTETRICS & GYNECOLOGY Alvero, R., Siedhoff, M., Clark, N. 2023; 35 (4)

  View details for DOI 10.1097/GCO.0000000000000890

  View details for Web of Science ID 001123214200002

• The no-man's land of non-tubal ectopic and Cesarean section scar pregnancies. Fertility and sterility Alvero, R. 2023

  Abstract

  Non-tubal ectopic and C-section scar pregnancy are a relatively uncommon but potentially very dangerous conception event. If diagnosed early, they can be treated very effectively. C-section scar ectopic is unique in that expectant management may allow them to persist longer but overwhelmingly with catastrophic consequences. Reproductive endocrinologists are uniquely positioned to diagnose and treat NTEP/CCSP early, thereby avoiding long-term catastrophic consequences.

  View details for DOI 10.1016/j.fertnstert.2023.07.017

  View details for PubMedID 37506760

• RECONSIDERATION OF COVERAGE FOR MEDICALLY NECESSARY FERTILITY PRESERVATION IN A POST-ROE ERA. Pecoriello, J., Alvero, R., Bryant, M., Ketterl, T., Leavitt, A., Levine, J., Lofye, D., Morales, J., Smith, K., Sorto, G., Rayco, K., Reinecke, J. ELSEVIER SCIENCE INC. 2023: E36

  View details for Web of Science ID 001038561400065

• Oocyte and embryo cryopreservation in ART: past achievements and current challenges. Fertility and sterility Casciani, V., Monseur, B., Cimadomo, D., Alvero, R., Rienzi, L. 2023

  Abstract

  Cryopreservation has revolutionized the treatment of infertility and fertility preservation. This review summarizes the milestones that paved the way to the current routinary clinical implementation of this game-changing practice in ART. Still, evidence to support "the best practice" in cryopreservation is controversial and several protocol adaptations exist that were described and compared herein, such as cumulus-intact versus cumulus-free oocyte cryopreservation, artificial collapse, assisted hatching, closed versus open carriers, and others. A last matter of concern is whether cryo-storage duration may impact oocyte/embryo competence, but the current body of evidence in this regard is reassuring. From social and clinical perspectives, oocyte and embryo cryopreservation has evolved from an afterthought when assisted reproduction was intended for immediate pregnancy with supernumerary embryos of secondary interest to its current purpose which is primarily to preserve fertility long-term and more comprehensively allow for family planning. However, the initial consenting process which still is geared to short-term fertility care may no longer be relevant when the individuals that initially preserved the tissues have completed their reproductive journey. A more encompassing counseling model is required to address changing patient values over time.

  View details for DOI 10.1016/j.fertnstert.2023.06.005

  View details for PubMedID 37290552

• Reproductive endocrinologist and infertility specialists' knowledge, skills, behaviors, and attitudes regarding the care for transgender and gender-diverse individuals. F&S reports Lipkin, P., Monseur, B., Mayo, J., Moravek, M., Nahata, L., Amato, P., Alvero, R., Obedin-Maliver, J. 2023; 4 (2): 213-223

  Abstract

  Objective: To investigate associations between reproductive endocrinology and infertility (REI) providers' prior training and current knowledge, skills, attitudes, and behaviors regarding fertility preservation and family building for transgender and gender-diverse (T/GD) patients.Design: The survey was distributed to members of the Society for Reproductive Endocrinology and Infertility, the REI-physician-focused professional body within the American Society for Reproductive Medicine, with additional participants recruited through snowball sampling.Results: Participants (n = 206) reported on training in T/GD care; 51% endorsed prior training. Most participants (93%) believed T/GD individuals were as fit for parenthood as cisgender individuals. Prior training was associated with an increased likelihood of offering T/GD health resources and more frequent consultations with specialist colleagues.Common barriers to providing care indicated by respondents included cost, delays in gender-affirming care, and lack of knowledge of the potential impact of hormonal interventions. Common facilitators included education and training, prior experience, and affordability of services.Conclusions: Most REI providers believed T/GD individuals are fit for parenthood and agreed that prior training facilitates care for T/GD patients. The lack of provider knowledge emerged as a barrier to care. Although training helped facilitate some components of care, systemic barriers such as the cost and variability of patient population characteristics/experiences are important considerations when serving T/GD individuals.

  View details for DOI 10.1016/j.xfre.2023.03.009

  View details for PubMedID 37398621

• Reproduction as the foundation for a healthy society. Fertility and sterility Alvero, R., Norman, R. J., Barnhart, K. T. 2023

  View details for DOI 10.1016/j.fertnstert.2023.05.004

  View details for PubMedID 37169325

• POSTER SESSION D: PILOT STUDY OF 'ROADMAP TO PARENTHOOD' DECISION AID AND PLANNING TOOL FOR FAMILY BUILDING AFTER CANCER Benedict, C., Simon, P., Spiegel, D., Kurian, A. W., Alvero, R., Berek, J. S., Philip, E. J., Schapira, L. OXFORD UNIV PRESS INC. 2023: S533

  View details for Web of Science ID 001042977901464

• ChatGPT: Rumors of Human Providers' Demise Have Been Greatly Exaggerated. Fertility and sterility Alvero, R. 2023

  View details for DOI 10.1016/j.fertnstert.2023.03.010

  View details for PubMedID 36921837

• Cost-effectiveness of IVF with PGT-M/A to prevent transmission of spinal muscular atrophy in offspring of carrier couples. Journal of assisted reproduction and genetics Khorshid, A., Boyd, A. L., Behr, B., Zhao, Q., Alvero, R., Bavan, B. 2023

  Abstract

  To evaluate the cost-effectiveness of in-vitro fertilization with preimplantation genetic testing for aneuploidy and monogenic disorders (IVF with PGT-M/A) to prevent transmission of spinal muscular atrophy to offspring of carrier couples.A decision-analytic model was created to compare the cost-effectiveness of IVF with PGT-M/A to unassisted conception with prenatal diagnostic testing and termination (if applicable). IVF with PGT-M/A costs were determined using a separate Markov state-transition model. IVF outcomes data was derived from 76 carriers of monogenic disorders who underwent IVF with PGT-M/A at a single academic REI center. Other probabilities, costs, and utilities were derived from the literature. Costs were modeled from healthcare perspective. Utilities were modeled from the parental perspective as quality-adjusted life-years (QALYs).The incremental cost-effectiveness ratio for IVF with PGT-M/A compared to unassisted conception is $22,050 per quality-adjusted life-year. The average cost of IVF with PGT-M/A is $41,002 (SD: $8,355). At willingness-to-pay thresholds of $50,000 and $100,000, IVF with PGT-M/A is cost-effective 93.3% and 99.5% of the time, respectively.Compared to unassisted conception, IVF with PGT-M/A is cost-effective for preventing the transmission of spinal muscular atrophy to the offspring of carrier couples. These findings support insurance coverage of IVF with PGT-M/A for carriers of spinal muscular atrophy.

  View details for DOI 10.1007/s10815-023-02738-7

  View details for PubMedID 36757555

• Assessment of patients' perceptions towards embryo disposition after donation of embryos to a research biobank. Journal of assisted reproduction and genetics Khorshid, A., Wignarajah, A., Zhang, J., Alvero, R., Lathi, R. B., Behr, B., Murugappan, G. 2022

  Abstract

  PURPOSE: To explore perceptions towards embryo disposition among patients donating excess embryos to a research biobank.METHODS: Cross-sectional study of survey responses collected as part of enrollment in a research biobank. Patients are asked questions regarding the difficulty of their disposition decision, their alternative disposition choice if donation to research was not available, quality of the counseling they received, and if additional counseling throughout their treatment would have been beneficial. Survey responses use 5-point Likert scales, with "1" being lowest/least and "5" being highest/most.RESULTS: A total of 157 men and 163 women enrolled in the biobank. Median scores for difficulty of disposition decision were 3 for females and 2 for males, and for quality of counseling, the median scores were 4 for females and 3 for males. Seventy percent of patients would have chosen to discard their excess embryos had donation to research not been an option. Statistical analyses showed no significant difference in responses based on variations in race, religion, sexual orientation, and infertility diagnoses. Concordance of responses within heterosexual couples was tested and found to be poor to moderate.CONCLUSIONS: Assessing patients' perceptions towards embryo disposition after donation of their excess embryos to a research biobank affords a unique perspective. The difficulty of the disposition decision, the tendency to discard embryos in the absence of a means for donation to research, and the poor agreement between heterosexual partners highlight the importance of donation to research as an accessible disposition option and the need for a personalized approach to counseling and consenting for embryo disposition.

  View details for DOI 10.1007/s10815-022-02659-x

  View details for PubMedID 36401676

• ASSESSMENT OF PATIENTS' ATTITUDES TOWARDS EMBRYO DONATION FOR RESEARCH. Khorshid, A., Wignarajah, A., Alvero, R., Lathi, R. B., Behr, B., Murugappan, G. ELSEVIER SCIENCE INC. 2022: E17-E18

  View details for Web of Science ID 000891942500024

• MORE RISK THAN REWARD: A COST ANALYSIS OF THE AMIGOS TRIAL Cardozo, E. R., Alvero, R. J., Diamond, M. P., Santoro, N., Bavan, B. ELSEVIER SCIENCE INC. 2022: E330

  View details for Web of Science ID 000891804601077

• Implementation of a comprehensive fertility biobanking initiative. F&S science Wignarajah, A., Alvero, R., Lathi, R. B., Aghajanova, L., Eisenberg, M., Winn, V. D., Behr, B., Murugappan, G. 2022; 3 (3): 228-236

  Abstract

  OBJECTIVE: To present the framework of Stanford Fertility and Reproductive Health's comprehensive reproductive biobanking initiatives and the results of the first year of recruitment.DESIGN: Technical description article.SETTING: Academic fertility center.PATIENT(S): Fertility patients >18 years of age.INTERVENTION(S): Enroll the patients interested in research in biobanking protocols.MAIN OUTCOME MEASURE(S): Patient recruitment and sample inventory from September 2020 to September2021.RESULT(S): A total of 253 patients have enrolled in the Stanford Fertility and Reproductive Health biobanking initiatives since September 2020. The current inventory consists of 1,176 samples, including serums, plasmas, buffy coats, endometria, maternal deciduae, miscarriage chorionic villi, and human embryos (zygote, cleavage, and blastocyst stages).CONCLUSION(S): This biobanking initiative addresses a critical, unmet need in reproductive health research to make it possible for patients to donate excess embryos and gametes and preserves, for future research, valuable somatic and reproductive tissues that would otherwise be discarded. We present the framework of this biobanking initiative in order to support future efforts of establishing similar biorepositories.

  View details for DOI 10.1016/j.xfss.2022.01.001

  View details for PubMedID 35977803

• The third degree: climate change and reproductive health. Fertility and sterility Alvero, R. 2022

  Abstract

  Climate change is a public health emergency, yet the medical community has been inconsistent in its understanding and engagement of the crisis. Reproductive endocrinology and infertility and reproductive biology will be impacted broadly by the changing climate. This Views and Reviews hopes to enlist reproductive endocrinology and infertility specialists to first understand the issues and then take action to support mitigation and accommodation efforts.

  View details for DOI 10.1016/j.fertnstert.2022.06.014

  View details for PubMedID 35786303

• Who needs experts? I'm doing my own research. Fertility and sterility Alvero, R. 2022

  View details for DOI 10.1016/j.fertnstert.2022.04.008

  View details for PubMedID 35534291

• Is telehealth a valuable resource in reproductive endocrinology and infertility? Fertility and sterility Parry, J. P., Chen, S. H., Ku, L., Anderson, K., Keller, S. L., Omurtag, K., Alvero, R. 2022; 117 (4): 690-695

  View details for DOI 10.1016/j.fertnstert.2022.02.001

  View details for PubMedID 35367014

• Do I really need to see my doctor? A changing paradigm in the physician-patient relationship in the time of COVID-19 and telehealth. Fertility and sterility Alvero, R. 2022; 117 (4): 688-689

  View details for DOI 10.1016/j.fertnstert.2022.02.002

  View details for PubMedID 35367013

• Effectiveness of Non-Surgical Management of Non-Tubal Ectopic Pregnancies in a Fertility Practice. Strug, M., Deng, J., Monseur, B., Alvero, R., Aghajanova, L. SPRINGER HEIDELBERG. 2022: 262-263

  View details for Web of Science ID 000762765300556

• AVERAGE COST OF IN VITRO FERTILIZATION WITH PREIMPLANTATION GENETIC TESTING FOR MONOGENIC DISORDERS AND ANEUPLOIDY PER UNAFFECTED LIVE BIRTH FOR CARRIER COUPLES. Khorshid, A., Boyd, A. H., Behr, B., Zhao, Q., Alvero, R. J., Bavan, B. ELSEVIER SCIENCE INC. 2021: E374-E375

  View details for Web of Science ID 000699951501421

• HIGH GROUNDWATER ARSENIC CONTAMINATION IS ASSOCIATED WITH STILLBIRTH, RECURRENT PREGNANCY LOSS, AND INFERTILITY: A POPULATION-BASED STUDY IN INDIA OF 643,944 REPRODUCTIVE AGED WOMEN. Monseur, B. C., Pinchoff, J., Koons, K., Desai, S., Alvero, R. J., Hindin, M. J. ELSEVIER SCIENCE INC. 2021: E91

  View details for Web of Science ID 000699951500208

• A DECISION MODEL PREDICTING THE SUCCESS AND COST OF IVF USING FROZEN BANKED VERSUS FRESH DIRECTED DONOR OOCYTES. Beshar, I., Deng, J., Alvero, R. J., Bavan, B. ELSEVIER SCIENCE INC. 2021: E32

  View details for Web of Science ID 000699951500076

• COST-EFFECTIVENESS OF IN VITRO FERTILIZATION WITH PREIMPLANTATION GENETIC TESTING TO PREVENT TRANSMISSION OF SPINAL MUSCULAR ATROPHY. Khorshid, A., Boyd, A. H., Behr, B., Zhao, Q., Alvero, R. J., Bavan, B. ELSEVIER SCIENCE INC. 2021: E373-E374

  View details for Web of Science ID 000699951501418

• The impact of the Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) pandemic on reproductive endocrinology. Current opinion in obstetrics & gynecology Alvero, R. 2021

  View details for DOI 10.1097/GCO.0000000000000740

  View details for PubMedID 34402482

• Surgical treatment of uterine septum to improve reproductive outcomes - resect or not? Fertility and sterility Alvero, R., Burney, R. O., Khorshid, A., Saravanabavanandhan, B., Pier, B. D., Rosalik, K. F., Schlaff, W. D. 2021

  View details for DOI 10.1016/j.fertnstert.2021.06.009

  View details for PubMedID 34274115

• Development and validation of a risk prediction index for severe maternal morbidity based on preconception comorbidities among infertile patients. Fertility and sterility Murugappan, G., Alvero, R. J., Lyell, D. J., Khandelwal, A., Leonard, S. A. 2021

  Abstract

  OBJECTIVE: To develop and validate a preconception risk prediction index for severe maternal morbidity (SMM), defined by the Centers for Disease Control and Prevention as indicators of a life-threatening complication, among infertile patients.DESIGN: Retrospective analysis of live births and stillbirths from 2007 to 2017 among infertile women.SETTING: National commercial claims database.PATIENT(S): Infertile women identified on the basis of diagnosis, testing, or treatment codes.INTERVENTION(S): None.MAIN OUTCOME MEASURE(S): The primary outcome was SMM, identified as any indicator from the Centers for Disease Control and Prevention Index except blood transfusion alone, which was found to overestimate cases. Twenty preconception comorbidities associated with a risk of SMM were selected from prior literature. Targeted ensemble learning methods were used to rank the importance of comorbidities as potential risk factors for SMM. The independent strength of the association between each comorbidity and SMM was then used to define each comorbidity's risk score.RESULT(S): Among 94,097 infertile women with a delivery, 2.3% (n = 2,181) experienced an SMM event. The highest risk of SMM was conferred by pulmonary hypertension, hematologic disorders, renal disease, and cardiac disease. Associated significant risks were lowest for substance abuse disorders, prior cesarean section, age ≥40 years, gastrointestinal disease, anemia, mental health disorders, and asthma. The receiver operating characteristic area under the curve for the developed comorbidity score was 0.66. Calibration plots showed good concordance between the predicted and actual risk of SMM.CONCLUSION(S): We developed and validated an index to predict the probability of SMM on the basis of preconception comorbidities in patients with infertility. This tool may inform preconception counseling of infertile women and support maternal health research initiatives.

  View details for DOI 10.1016/j.fertnstert.2021.06.024

  View details for PubMedID 34266662

• Association of Infertility and All-Cause Mortality: Analysis of US Claims Data. American journal of obstetrics and gynecology Murugappan, G. n., Li, S. n., Alvero, R. J., Luke, B. n., Eisenberg, M. L. 2021

  Abstract

  The consequences of an infertility diagnosis extend beyond the pursuit of family building, as infertile women also face increased risks of severe maternal morbidity, cancer, and chronic disease.To examine the association between female infertility and all-cause mortality.Retrospective analysis of 72,786 infertile women identified in the Optum Clinformatics Datamart from 2003-2019 by infertility diagnosis, testing and treatment codes compared with 3,845,790 non-infertile women seeking routine gynecologic care. Baseline comorbidities were assessed using the presence of ≥1 metabolic syndrome (MetS) diagnoses and the Charlson Comorbidity Index (CCI). The primary outcome of all-cause mortality was identified by linkage to Social Security Administration Death Master File outcomes and medical claims. The association of infertility with mortality was examined using Cox proportional hazard regression while adjusting for age, hypertension, hyperlipidemia, type II diabetes, year of evaluation, smoking, number of visits per year, nulliparity, obesity, region of country, and race.Among 16,473,458 person-years of follow up, 13,934 women died. Infertile women had a 32% higher relative risk of death from any cause (0.42% versus 0.35%, aHR 1.32, 95% CI 1.18-1.48) compared to non-infertile women. Mean follow up time per patient was 4.0±3.7 years versus 4.2±3.8 years for infertile and non-infertile women, respectively. When stratified by age < 35 or ≥35 years or baseline medical comorbidity, the association between infertility and mortality remained. Infertile women who delivered a child during the follow up period faced similar increased risk of mortality compared to the overall infertile group. Finally, receipt of fertility treatment was not associated with a higher risk of death compared to receiving an infertility diagnosis or testing alone.While absolute risk of death was low in both groups, infertile women faced a higher relative risk of mortality compared to non-infertile women. The association remained across all age, race/ethnicity, morbidity, and delivery strata. Importantly, infertility treatment was not associated with an increased risk of death. These findings reinforce the disease burden associated with infertility and its potential for longer-term sequelae.

  View details for DOI 10.1016/j.ajog.2021.02.010

  View details for PubMedID 33577764

• Is living in a region with high groundwater arsenic contamination associated with adverse reproductive health outcomes? An analysis using nationally representative data from India. International journal of hygiene and environmental health Pinchoff, J., Monseur, B., Desai, S., Koons, K., Alvero, R., Hindin, M. J. 2021; 239: 113883

  Abstract

  Exposure to groundwater arsenic via drinking water is common in certain geographies, such as parts of India, and causes a range of negative health effects, potentially including adverse reproductive health outcomes.We conducted an ecological analysis of self-reported rates of stillbirth, recurrent pregnancy loss, and infertility in relation to groundwater arsenic levels in India. We used a gridded, modeled dataset of the probability of groundwater arsenic exceeding 10 μg/L (World Health Organization drinking water limit) to calculate mean probabilities at the district level (n = 599 districts). A spatial integration approach was used to merge these estimates with the third India District-Level Health Survey (DLHS-3) conducted in 2007-08 (n = 643,944 women of reproductive age). Maps of district level arsenic levels and rates of each of the three outcomes were created to visualize the patterns across India. To adjust for significant spatial autocorrelation, spatial error models were fit.District-level analysis showed that the average level of stillbirth was 4.3%, recurrent pregnancy loss was 3.3%, and infertility was 8.1%. The average district-level probability of groundwater arsenic levels exceeding 10 μg/L was 42%. After adjustment for sociodemographic factors, and accounting for spatial dependence, at the district level, for each percentage point increase in predicted arsenic levels exceeding 10 μg/L increased, the rates of stillbirths was 4.5% higher (95% confidence interval (CI) 2.4-6.6, p < 0.0001), the rates of RPL are 4.2% higher (95% CI 2.5-5.9, p < 0.0001), and the rates of infertility are 4.4% higher (95% CI 1.2-7.7, p=<0.0001).).While arsenic exposure has been implicated with a range of adverse health outcomes, this is one of the first population-level studies to document an association between arsenic and three adverse reproductive pregnancy outcomes. The high levels of spatial correlation suggest that further and targeted efforts to mitigate arsenic in groundwater are needed.

  View details for DOI 10.1016/j.ijheh.2021.113883

  View details for PubMedID 34837822

• It was the best of times; it was the worst of times: the impact of the SARS-CoV2 (COVID-19) pandemic on reproductive endocrinology. Current opinion in obstetrics & gynecology Alvero, R. 2021

  Abstract

  To review the impact that COVID-19 has had on the practice of reproductive endocrinology and infertility.As in all areas of medicine, the COVID-19 pandemic has caused profound changes in reproductive endocrinology and infertility. However, the pandemic has encouraged providers and systems to change approaches and unmasked many opportunities that may have actually improved care. The pandemic also forced the field to provide society with fact-based information even as data was constantly emerging and evolving and to do so rapidly.Combating misinformation became an equally important effort and led to increased participation of providers using traditional and social media to provide the most reliable and up to date information. A return to status quo ante bellum is unlikely.

  View details for DOI 10.1097/GCO.0000000000000730

  View details for PubMedID 34101662

• Natural vs. programmed cycles for frozen embryo transfer: study protocol for an investigator-initiated, randomized, controlled, multicenter clinical trial. Trials Baksh, S., Casper, A., Christianson, M. S., Devine, K., Doody, K. J., Ehrhardt, S., Hansen, K. R., Lathi, R. B., Timbo, F., Usadi, R., Vitek, W., Shade, D. M., Segars, J., Baker, V. L. 2021; 22 (1): 660

  Abstract

  Randomized trials of assisted reproductive technology (ART) have been designed for outcomes of clinical pregnancy or live birth and have not been powered for obstetric outcomes such as preeclampsia, critical for maternal and fetal health. ART increasingly involves frozen embryo transfer (FET). Although there are advantages of FET, multiple studies have shown that risk of preeclampsia is increased with FET compared with fresh embryo transfer, and the reason for this difference is not clear. NatPro will compare the proportion of preeclampsia between two commonly used protocols for FET,modified natural and programmed cycle.In this two-arm, parallel-group, multi-center randomized trial, NatPro will randomize 788 women to either modified natural or programmed FET and follow them for up to three FET cycles. Primary outcome will be the proportion of preeclampsia in women with a viable pregnancy assigned to a modified natural cycle FET (corpus luteum present) protocol compared to the proportion of preeclampsia in pregnant women assigned to a programmed FET (corpus luteum absent) protocol. Secondary outcomes will compare the proportion of live births and the proportion of preeclampsia with severe features between the protocols.This study has a potential significant impact on millions of women who pursue ART to build their families. NatPro is designed to provide clinically relevant guidance to inform patients and clinicians regarding maternal risk with programmed and modified natural cycle FET protocols. This study will also provide accurate point estimates regarding the likelihood of live birth with programmed and modified natural cycle FET.ClinicalTrials.gov NCT04551807 . Registered on September 16, 2020.

  View details for DOI 10.1186/s13063-021-05637-3

  View details for PubMedID 34579768

• PRE-CONCEPTION RISK PREDICTION INDEX FOR SEVERE MATERNAL MORBIDITY AMONG INFERTILE WOMEN. Murugappan, G., Alvero, R. J., Lyell, D. J., Khandelwal, A., Leonard, S. A. ELSEVIER SCIENCE INC. 2020: E65

  View details for Web of Science ID 000579355300157

• ASSOCIATION BETWEEN INFERTILITY AND MORTALITY: ANALYSIS OF US CLAIMS DATA. Murugappan, G., Li, S., Alvero, R. J., Eisenberg, M. L. ELSEVIER SCIENCE INC. 2020: E50–E51

  View details for Web of Science ID 000579355300122

• Consenting and ethical considerations in embryo cryopreservation. Current opinion in obstetrics & gynecology Khorshid, A., Alvero, R. 2020

  Abstract

  PURPOSE OF REVIEW: An emerging body of literature has elucidated the growing burden of surplus embryos left in storage without any clear disposition. An out dated consent process is a significant but easily remedied contributor to this problem. We propose a novel approach to consenting for disposition of surplus embryos.RECENT FINDINGS: Decisional conflicts that stem from the moral status of embryos and from evolving personal values contribute to surplus embryos being left in storage. Barriers to donation of embryos to research or to other patients also discourage embryo disposition decisions. A flawed informed consent process compromises the physician--provider relationship and complicates decision-making.SUMMARY: Centralizing the process of donating embryos to research and to patients would lower barriers to these disposition options. The informed consent protocol must be redesigned as a longitudinal, narrative process compatible with the evolving values and fertility outcomes of patients. Counselors should be integrated into all discussions regarding embryo disposition from the onset of fertility treatment through its conclusion to facilitate the decision-making process.

  View details for DOI 10.1097/GCO.0000000000000653

  View details for PubMedID 32739976

• Challenging topics in reproductive endocrinology. Current opinion in obstetrics & gynecology Alvero, R. 2020

  View details for DOI 10.1097/GCO.0000000000000652

  View details for PubMedID 32739975

• Compassionate embryo transfer: part of a bigger question. Fertility and sterility Monseur, B., Alvero, R. J., Schlaff, W. D. 2020

  View details for DOI 10.1016/j.fertnstert.2020.05.037

  View details for PubMedID 32654819

• Improving the fellowship interview experience for reproductive endocrinology and infertility candidates: a survey. F&S reports New, E. P., Sarkar, P., Alvero, R. J., Imudia, A. N. 2020; 1 (1): 37-42

  Abstract

  To collect data on the current reproductive endocrinology and infertility (REI) fellowship interview process so that it may be improved in the future.Web-based cross-sectional survey. In addition, fellowship program directors and coordinators were contacted by e-mail.Survey data were collected after completion of the 2018 REI fellowship interview season.Not applicable.None.Number of days used for interviews, missed opportunities to interview, frequency of travel to the same city, average money spent, recommendations for how the interview process could be improved.There were 44 survey respondents. The mean number of interviews attended was 12.6 (range, 1-22). On average 13.4 (0-30) days off work were used to interview. About 68.1% (n = 30) missed an opportunity to interview at a program they were interested in. The most common reasons were the interview date was the same day as another interview, could not attend due to geographic location, and cost was too high. About 72% (n = 31) traveled to the same city more than once for an interview. The average cost per interview was $478 (range, $200-$1,000) and average cost per interview season was $5,660 (range, $900-$15,000). Fellowship program data were available from 43 of 48 programs contacted. The number of dates that had conflicting interviews scheduled were 26.These data highlight the need to coordinate the REI fellowship recruitment process between programs to reduce conflicting interview dates and mitigate costs to applicants. Based on these results, a concrete action plan is presented.

  View details for DOI 10.1016/j.xfre.2020.03.004

  View details for PubMedID 34223210

  View details for PubMedCentralID PMC8244322

• Is intracytoplasmic sperm (ICSI) better than traditional in vitro fertilization (IVF): confirmation of higher blastocyst rates per oocyte using a split insemination design. Journal of assisted reproduction and genetics Sauerbrun-Cutler, M., Huber, W. J., Has, P., Shen, C., Hackett, R., Alvero, R., Wang, S. 2020

  Abstract

  PURPOSE: To explore the effects of traditional vs. intracytoplasmic sperm injection (ICSI) insemination method on the outcome of high-quality blastocyst development in a split sibling oocyte cohort.METHODS: In this retrospective cohort study, we analyzed 62 ICSI/IVF split cycles. Sibling oocytes were randomly assigned to ICSI or IVF insemination. Two hundred thirty-four ICSI-only cycles and 152 IVF-only cycles were also analyzed for comparison. Blastocysts were graded by Gardner's embryo grading and were considered a high-quality blastocyst if 3BB or better (Gardner 1999).RESULTS: In the ICSI/IVF split group, (1) ICSI oocytes had a higher fertilization rate per oocyte allocated (73% vs 62%, p < 0.001), (2) more high-quality day 2 embryos (69% vs 55%, p < 0.005), (3) ICSI oocytes had a lower blastulation rate per 2PN (46% vs 54%, p < 0.05), but a higher blastulation rate when calculated per oocyte allocated (40% vs 32%, p < 0.05). The ICSI-only group had a lower fertilization rate (65% vs 70%, p < 0.001) but more high-quality day 2 embryos in comparison to the IVF-only group (68% vs 64%, p < .05). The total high-quality blastulation rate was higher for the IVF-only group per 2PN (49% vs 43%, p < 0.05) and per oocyte retrieved (34% vs 28%, p < 0.05).CONCLUSIONS: This distinctive IVF/ICSI sibling oocyte split design demonstrated a higher-quality blastulation rate in the IVF group compared to the ICSI group when calculated per 2PN, but not per oocyte allocated to each insemination procedure.

  View details for DOI 10.1007/s10815-020-01819-1

  View details for PubMedID 32436048

• Pregnancy registry: three-year follow-up of children conceived from letrozole, clomiphene, or gonadotropins. Fertility and sterility Legro, R. S., Diamond, M. P., Coutifaris, C., Schlaff, W. D., Alvero, R., Casson, P., Christman, G. M., Rosen, R. M., Cedars, M. I., Hansen, K. R., Robinson, R., Baker, V., Usadi, R., Dodson, W. C., Estes, S. J., Kunselman, A., Stetter, C., Barnhart, K. T., Coward, R. M., Trussell, J. C., Krawetz, S. A., Santoro, N., Huang, H., Zhang, H., Eisenberg, E., Reproductive Medicine Network 2020; 113 (5): 1005–13

  Abstract

  OBJECTIVE: To study the development of children conceived from non-IVF infertility treatments consisting of gonadotropins, clomiphene, or letrozole.DESIGN: Prospective cohort study.SETTING: U.S. academic health centers.PATIENT(S): Children of women with polycystic ovary syndrome who conceived with letrozole (LTZ) or clomiphene (CC) in the PPCOS II study or women with unexplained infertility (AMIGOS study) who conceived with LTZ, CC, or gonadotropin (GN).INTERVENTION(S): Longitudinal annual follow-up from birth to age3.MAIN OUTCOME MEASURE(S): Scores from Ages and Stages Developmental Questionnaire (ASQ), MacArthur-Bates Communicative Development Inventory (MCDI), and annual growth.RESULT(S): One hundred eighty-five children from 160 families participated in at least one follow-up evaluation from the two infertility trials. Most multiple gestations in the follow-up study resulted from GN treatment (n = 14) followed by CC (n = 6) and LTZ (n = 3). There were no significant differences among the three groups at any time point with respect to abnormal scores on the ASQ. On the MCDI Words and Gestures, the LTZ group scored significantly higher than the GN group for most items (phrases, early gestures, later gestures, and total gestures). Children in the CC group scored significantly higher than the GN group for the later gestures and total gestures items.CONCLUSION(S): Differences in growth and cognitive developmental rates among children conceived with first-line infertility therapies, including LTZ, are relatively minor and likely due to differences in multiple pregnancy rates.

  View details for DOI 10.1016/j.fertnstert.2019.12.023

  View details for PubMedID 32386612

• Publisher Correction: Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nature communications Hayes, M. G., Urbanek, M., Ehrmann, D. A., Armstrong, L. L., Lee, J. Y., Sisk, R., Karaderi, T., Barber, T. M., McCarthy, M. I., Franks, S., Lindgren, C. M., Welt, C. K., Diamanti-Kandarakis, E., Panidis, D., Goodarzi, M. O., Azziz, R., Zhang, Y., James, R. G., Olivier, M., Kissebah, A. H., Reproductive Medicine Network, Stener-Victorin, E., Legro, R. S., Dunaif, A., Alvero, R., Barnhart, H. X., Baker, V., Barnhart, K. T., Bates, G. W., Brzyski, R. G., Carr, B. R., Carson, S. A., Casson, P., Cataldo, N. A., Christman, G., Coutifaris, C., Diamond, M. P., Eisenberg, E., Gosman, G. G., Giudice, L. C., Haisenleder, D. J., Huang, H., Krawetz, S. A., Lucidi, S., McGovern, P. G., Myers, E. R., Nestler, J. E., Ohl, D., Santoro, N., Schlaff, W. D., Snyder, P., Steinkampf, M. P., Trussell, J. C., Usadi, R., Yan, Q., Zhang, H. 2020; 11 (1): 2158

  Abstract

  An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  View details for DOI 10.1038/s41467-020-15793-w

  View details for PubMedID 32345980

• Building a strong reproductive endocrinology and infertility fellowship foundation will lead to better care and future success. Fertility and sterility Coddington, C. C., Alvero, R. 2020; 113 (3): 551

  View details for DOI 10.1016/j.fertnstert.2019.12.021

  View details for PubMedID 32192590

• Androgenicity and fertility treatment in women with unexplained infertility. Fertility and sterility Wang, E. T., Diamond, M. P., Alvero, R., Casson, P., Christman, G. M., Coutifaris, C., Hansen, K. R., Sun, F., Legro, R. S., Robinson, R. D., Usadi, R. S., Pisarska, M. D., Santoro, N. F., Zhang, H. 2020; 113 (3): 636-641

  Abstract

  To determine whether biochemical or clinical markers of androgenic activity predict live birth rate with ovarian stimulation in the unexplained infertility population.Secondary analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial.Multicenter university-based clinical practices.Nine hundred couples with unexplained infertility were included. Women were 18-40 years old with regular menses, a normal uterine cavity, at least one patent fallopian tube, and a male partner with ≥5 million motile sperm. Women were randomized to receive gonadotropin, clomiphene, or letrozole with IUI for four or fewer four treatment cycles. Women were evaluated for biochemical (total testosterone, DHEAS, and free androgen index) and clinical markers of androgenic activity (sebum, acne, and hirsutism). Multivariable logistic regression models adjusting for treatment group, maternal age, and body mass index were performed.None.The primary outcome was live birth. Secondary outcomes included conception, clinical pregnancy, and pregnancy loss.When comparing 900 women in the AMIGOS trial based on quartiles of serum TT, women were of younger age, higher body mass index, and higher waist circumference with increasing TT. Increasing quartiles of TT also showed increasing DHEAS and free androgen index values. Serum androgens were not associated with outcomes of live birth, conception, clinical pregnancy, or pregnancy loss. Clinical androgen markers were not associated with pregnancy outcomes.In a randomized cohort of women with unexplained infertility, biochemical and clinical measures of androgens did not predict live birth rate after ovarian stimulation treatment.NCT 01044862.

  View details for DOI 10.1016/j.fertnstert.2019.10.034

  View details for PubMedID 32192596

  View details for PubMedCentralID PMC7088440

• Intrauterine insemination performance characteristics and post-processing total motile sperm count in relation to live birth for couples with unexplained infertility in a randomised, multicentre clinical trial. Human reproduction (Oxford, England) Hansen, K. R., Peck, J. D., Coward, R. M., Wild, R. A., Trussell, J. C., Krawetz, S. A., Diamond, M. P., Legro, R. S., Coutifaris, C. n., Alvero, R. n., Robinson, R. D., Casson, P. n., Christman, G. M., Santoro, N. n., Zhang, H. n., Medicine Network, F. T. 2020

  Abstract

  Are intrauterine insemination (IUI) performance characteristics and post-processing total motile sperm count (TMC) related to live birth rate in couples with unexplained infertility?Patient discomfort with IUI and lower inseminate TMC were associated with a reduced live birth rate, while time from hCG injection to IUI, sperm preparation method and ultrasound guidance for IUI were not associated with live birth success.We previously determined that some baseline characteristics of couples with unexplained infertility, including female age, duration of infertility, history of prior loss and income, were related to live birth rate across a course of ovarian stimulation and IUI treatment. However, the relationship between treatment outcomes and per-cycle characteristics, including ultrasound guidance for IUI, timing of IUI relative to hCG injection, difficult or painful IUI and inseminate TMC, are controversial, and most prior investigations have not evaluated live birth outcome.This was a secondary analyses of 2462 cycles from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. This prospective, randomised, multicentre clinical trial determined live birth rates following IUI after ovarian stimulation with clomiphene citrate, letrozole or gonadotropins in 854 couples with unexplained infertility. It was conducted between 2011 and 2014, and couples could undergo up to four consecutive treatment cycles.AMIGOS was an NIH-sponsored Reproductive Medicine Network trial conducted at 12 clinical sites. Participants were women with unexplained infertility who were between 18 and 40 years of age. Cluster-weighted generalised estimating equations (GEE), which account for informative clustering of multiple IUI treatment cycles within the same patient, were used to determine associations between IUI performance characteristics, including inseminate TMC, and live birth rate. Efficiency curves were also generated to examine the relationship between inseminate TMC and live birth rate.After adjustment for treatment group and baseline factors previously associated with live birth across a course of OS-IUI treatment, patient discomfort during the IUI procedure was associated with a reduction in live birth rate (aRR 0.40 (0.16-0.96)). Time from hCG trigger injection to IUI was not significantly associated with outcome. Higher TMC was associated with greater live birth rate (TMC 15.1-20.0 million (14.8%) compared to ≤5 million (5.5%)) (aRR 2.09 (1.31-3.33)). However, live births did occur with TMC ≤ 1 million (5.1%).This investigation is a secondary analysis, and AMIGOS was not designed to address the present question. Since timed intercourse was allowed as part of the AMIGOS trial, we cannot rule out the possibility that any given pregnancy resulted from intercourse rather than IUI.Most factors associated with the performance of IUI were not significantly related to obtaining live birth. Our findings suggest that higher TMC inseminated leads to an increase in live birth rate up to TMC ~20 million. However, there may be no reasonable threshold below which live birth is not possible with IUI.Funding was received through grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10 HD055925. This research was made possible by funding by the American Recovery and Reinvestment Act. Dr Hansen reports grants from NIH/NICHD and Yale University during the conduct of the study, grants from Roche Diagnostics and grants from Ferring International Pharmascience Center US outside the submitted work. Dr Peck reports support from Ferring Pharmaceuticals outside the submitted work. Dr Coward has nothing to disclose. Dr Wild reports grants from NICHD during the conduct of the study. Dr Trussell has nothing to disclose. Dr Krawetz reports grants from NICHD during the conduct of the study, grants from Merck and support from Taylor and Frances and from Springer, outside the submitted work. Dr Diamond reports grants from NIH/NICHD, Yale University, during the conduct of the study and support from Advanced Reproductive Care AbbVie, Bayer and ObsEva, outside the submitted work. Dr Legro reports support from Bayer, Kindex, Odega, Millendo and AbbVie and grants and support from Ferring, outside the submitted work. Dr Coutifaris reports grants from NICHD/NIH and personal fees from American Society for Reproductive Medicine, outside the submitted work. Dr Alvero has nothing to disclose. Dr Robinson reports grants from NIH during the conduct of the study. Dr Casson has nothing to disclose. Dr Christman reports grants from NICHD during the conduct of the study. Dr Santoro reports grants from NIH during the conduct of the study. Dr Zhang reports grants from NIH during the conduct of the study and support from Shangdong University outside the submitted work.n/a.

  View details for DOI 10.1093/humrep/deaa027

  View details for PubMedID 32432326

• Direct Methotrexate Injection into the Gestational Sac for Nontubal Ectopic Pregnancy: A Review of Efficacy and Outcomes from a Single Institution. Journal of minimally invasive gynecology Gilbert, S. B., Alvero, R. J., Roth, L., Polotsky, A. J. 2020; 27 (1): 166-172

  Abstract

  To evaluate the efficacy of nontubal ectopic pregnancy (NTEP) management with direct methotrexate (MTX) injection into the gestational sac.A retrospective chart review.A tertiary academic and teaching hospital.All cases of confirmed NTEP were retrospectively identified from 2012 to 2017.Ultrasound-guided direct injection of MTX into the fetal pole and surrounding gestational sac and a single dose of systemic MTX with or without fetal intracardiac injection of potassium chloride.Treatment failure, complications from treatment, operating time, and days to negative serum human chorionic gonadotropin (hCG) after treatment were measured. Fourteen women (age 34 ± 5.2 years) with NTEP underwent direct MTX injection (cesarean scar, n = 4; interstitial, n = 6; cervical, n = 4). The mean estimated gestational age was 49 ± 11, CI (43, 56 days). One patient required laparoscopic intervention with a failure rate of 1 of 14 (a double interstitial, heterotopic pregnancy). There were no other major complications. The time in the operating room was similar for all NTEP types. The average time to negative serum hCG was not different for cesarean scar (84.5 ± 36 days), cervical pregnancies (70.5 ± 19 days), or interstitial pregnancies (45.3 ± 38 days, p = .15).Direct MTX injection into the gestational sac for NTEP treatment is safe and effective. The failure rate of 7% is considerably lower than what was previously reported for a failure of systemic MTX in similar cases (25%). Resolution of serum hCG after treatment can be quite prolonged even in uncomplicated cases.

  View details for DOI 10.1016/j.jmig.2019.03.016

  View details for PubMedID 30930212

• Short- and long-term impact of gonadotropin-releasing hormone analogue treatment on bone loss and fracture. Fertility and sterility Sauerbrun-Cutler, M., Alvero, R. 2019; 112 (5): 799–803

  Abstract

  Gonadotropin-releasing hormone analogues (GnRH-a) are commonly utilized in moderate to severe endometriosis to induce atrophy of endometriotic lesions. Unfortunately, cessation of therapy can lead to recurrence of symptoms. Therefore, long term therapy is sometimes necessary. GnRH analogues cause an immediate decrease in bone mineral density which usually recovers after cessation of its use. However, this recovery in bone mineral density may not always occur after long term use. In order to prevent the deleterious effects on bone, add-back therapy is used frequently. This review will explore the impact of GnRH analogues on both bone loss and fracture risk as well as describe different add-back regimens.

  View details for DOI 10.1016/j.fertnstert.2019.09.037

  View details for PubMedID 31731934

• THE UTILITY OF REPEAT SALINE INFUSION SONOHYSTEROGRAM (SIS) IN THE INFERTILITY WORKUP. Dolinko, A. V., Danilack, V. A., Alvero, R. J., Snegovskikh, V. V. ELSEVIER SCIENCE INC. 2019: E357

  View details for DOI 10.1016/j.fertnstert.2019.07.1024

  View details for Web of Science ID 000487821303148

• IMPROVING THE REI FELLOWSHIP INTERVIEW EXPERIENCE: A SURVEY. New, E. P., Sarkar, P., Alvero, R. J., Imudia, A. N. ELSEVIER SCIENCE INC. 2019: E97

  View details for DOI 10.1016/j.fertnstert.2019.07.374

  View details for Web of Science ID 000487821300236

• Fertility Related Quality of Life, Gonadal Function and Erectile Dysfunction in Male Partners of Couples with Unexplained Infertility JOURNAL OF UROLOGY Coward, R., Stetter, C., Kunselman, A., Trussell, J. C., Lindgren, M. C., Alvero, R. R., Casson, P., Christman, G. M., Coutifaris, C., Diamond, M. P., Hansen, K. R., Krawetz, S. A., Legro, R. S., Robinson, R. D., Smith, J. F., Steiner, A. Z., Wild, R. A., Zhang, H., Santoro, N., Reproductive Med Network 2019; 202 (2): 379–84

  Abstract

  We sought to determine whether lower fertility related quality of life or depression in men of couples with unexplained infertility is associated with low total testosterone levels, abnormal semen quality or erectile dysfunction.This study is a secondary analysis of a large, multicenter, randomized controlled trial in couples with unexplained infertility. Male partners underwent baseline semen analysis with measurement of fasting total testosterone and gonadotropin. They also completed surveys, including the FertiQOL (Fertility Quality of Life), the PHQ-9 (Patient Health Questionnaire-9) and the IIEF (International Index of Erectile Function). The primary study outcomes were total testosterone with low total testosterone defined as less than 264 ng/dl, semen parameters and the IIEF score. We performed multivariable logistic regression analyses adjusted for patient age, race, body mass index, education, smoking, alcohol use, infertility duration and comorbidity.A total of 708 men with a mean ± SD age of 34.2 ± 5.6 were included in study. Of the men 59 (8.3%) had a PHQ-9 score of 5 or greater, which was consistent with depression, 99 (14.0%) had low total testosterone and 63 (9.0%) had mild or worse erectile dysfunction. Neither the FertiQOL score nor depression was associated with total testosterone or any semen parameter. The FertiQOL score was inversely associated with erectile dysfunction (for every 5-point score decline AOR 1.30, 95% CI 1.16-1.46). Depressed men were significantly more likely to have erectile dysfunction than nondepressed men (AOR 6.31, 95% CI 3.12-12.77).In men in couples with unexplained infertility lower fertility related quality of life and depression are strongly associated with erectile dysfunction. However, neither is associated with spermatogenesis or testosterone levels. Erectile dysfunction in infertile men merits longitudinal investigation in future studies.

  View details for DOI 10.1097/JU.0000000000000205

  View details for Web of Science ID 000475859600046

  View details for PubMedID 30835629

• Cultural Experiences, Patterns, and Practices of American Indian Women With Polycystic Ovary Syndrome: An Ethnonursing Study. Journal of transcultural nursing : official journal of the Transcultural Nursing Society Carron, R., Kooienga, S., Gilman-Kehrer, E., Alvero, R. 2019: 1043659619856670

  Abstract

  Introduction: Knowledge is needed about the cultural experiences, patterns, and practices of American Indian women with polycystic ovary syndrome (PCOS), so nurses can provide culturally congruent care. Method: A qualitative, ethnonursing study based on Leininger's theory of culture care diversity and universality. Data were collected from 13 key informants living on a reservation in the Western United States. Data were analyzed with Leininger's four phases of qualitative analysis. Results: Three universal themes were identified: (1) control of PCOS symptoms is important for the cultural well-being of tribal women, (2) culturally congruent PCOS education and health care are important with variations in approaches to treatment, and (3) tribal culture is important with variations in use of tribal practices. Discussion: Tribal culture affects the health care beliefs and practices of American Indian women with PCOS. The findings can be used to improve culturally congruent care for women with this chronic condition.

  View details for DOI 10.1177/1043659619856670

  View details for PubMedID 31204601

• 3-D Ultrasound is Accurate for Follicular Monitoring But Does Not Reduce Time to Perform Sauerbrun, M., Ghidei, L., Huber, W. J., Wu, X., Alvero, R., Wang, S. LIPPINCOTT WILLIAMS & WILKINS. 2019: 209S–210S

  View details for DOI 10.1097/01.AOG.0000559479.77504.aa

  View details for Web of Science ID 000473810000723

• Using the Medicine Wheel Model to Study Polycystic Ovary Syndrome in American Indian Women. Research and theory for nursing practice Carron, R. n., Kooienga, S. n., Gilman-Kehrer, E. n., Alvero, R. n., Boyle, D. K. 2019; 33 (3): 246–56

  Abstract

  Developing a nursing research project with American Indian tribes and navigating the institutional review board approval process can appear daunting to investigators because of tribal research requirements in addition to academic requirements. Nurse investigators conducted a research project exploring experiences of American Indian women with polycystic ovary syndrome. After successful implementation of the project, a model emerged to guide researchers working with tribal communities through project development and the institutional review board process. The model is based on the American Indian medicine wheel with each quadrant aligned with a season of the year: spring, summer, fall, and winter. The seasonal approach divides project development into sections that can be developed independently or simultaneously. The model emphasizes collaborative relationships between the research team and tribe. Researchers can adapt and customize the model for their projects based on their objectives and targeted populations. The purpose of this article is to describe the medicine wheel model and, as an exemplar, demonstrate application of the model in a project involving American Indian women with polycystic ovary syndrome. Additionally, potential implications of the model for nursing research, education, and practice are presented.

  View details for DOI 10.1891/1541-6577.33.3.246

  View details for PubMedID 31615944

• Using the Medicine Wheel Model to Study Polycystic Ovary Syndrome in American Indian Women RESEARCH AND THEORY FOR NURSING PRACTICE Carron, R., Kooienga, S., Gilman-Kehrer, E., Alvero, R., Boyle, D. K. 2019; 33 (3): 246–56

  View details for DOI 10.1891/1541.6577.33.3.246

  View details for Web of Science ID 000505580900006

• Comparison of sonohysterography to hysterosalpingogram for tubal patency assessment in a multicenter fertility treatment trial among women with polycystic ovary syndrome JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Christianson, M. S., Legro, R. S., Jin, S., Eisenberg, E., Diamond, M. P., Hansen, K. R., Vitek, W., Styer, A. K., Casson, P., Coutifaris, C., Christman, G. M., Alvero, R., Puscheck, E. E., Christy, A. Y., Sun, F., Zhang, H., Polotsky, A. J., Santoro, N. 2018; 35 (12): 2173–80

  Abstract

  To compare saline infusion sonohysterography (SIS) versus hysterosalpingogram (HSG) for confirmation of tubal patency.Secondary analysis of a randomized controlled trial, Pregnancy in Polycystic Ovary Syndrome II (PPCOS II). Seven hundred fifty infertile women (18-40 years old) with polycystic ovary syndrome (PCOS) were randomized to up to 5 cycles of letrozole or clomiphene citrate. Prior to enrollment, tubal patency was determined by HSG, the presence of free fluid in the pelvis on SIS, laparoscopy, or recent intrauterine pregnancy. Logistic regression was conducted in patients who ovulated with clinical pregnancy as the outcome and HSG or SIS as the key independent variable.Among women who ovulated, 414 (66.9%) had tubal patency confirmed by SIS and 187 (30.2%) had at least one tube patent on HSG. Multivariable analysis indicated that choice of HSG versus SIS did not have a significant relationship on likelihood of clinical pregnancy, after adjustment for treatment arm, BMI, duration of infertility, smoking, and education (OR 1.14, 95% CI 0.77, 1.67, P = 0.52). Ectopic pregnancy occurred more often in women who had tubal patency confirmed by HSG compared to SIS (2.8% versus 0.6%, P = 0.02).In this large cohort of women with PCOS, there was no significant difference in clinical pregnancy rate between women who had tubal patency confirmed by HSG versus SIS. SIS is an acceptable imaging modality for assessment of tubal patency in this population.

  View details for DOI 10.1007/s10815-018-1306-2

  View details for Web of Science ID 000452869100011

  View details for PubMedID 30194618

  View details for PubMedCentralID PMC6289919

• Gestational Weight Gain in Women With Polycystic Ovary Syndrome: A Controlled Study. The Journal of clinical endocrinology and metabolism Kent, J., Dodson, W. C., Kunselman, A., Pauli, J., Stone, A., Diamond, M. P., Coutifaris, C., Schlaff, W. D., Alvero, R., Casson, P., Christman, G. M., Rosen, R. M., Hansen, K. R., Robinson, R. D., Baker, V., Usadi, R., Santoro, N., Zhang, H., Eisenberg, E., Legro, R. S., Reproductive Medicine Network 2018; 103 (11): 4315–23

  Abstract

  Context: Women with polycystic ovary syndrome (PCOS) have increased risk for pregnancy complications, possibly related to pre-existing obesity and excessive gestational weight gain (GWG).Objectives: To assess the contributions of diagnosis and preconception weight on GWG and perinatal outcomes.Research Design and Methods: Prospective cohort study of singleton pregnancies in PCOS (n = 164) and ovulatory controls (n = 176) from infertility treatment.Main Outcome Measures: GWG, birthweight, pregnancy complications.Results: From preconception baseline, normal-weight women with PCOS gained 2.3 pounds more during the first trimester (95% CI, 0.3 to 4.3; P = 0.02), and by the end of the second trimester, 4.2 pounds more than controls (95% CI, 0.7 to 7.7; P = 0.02). Women who were overweight with PCOS gained significantly more weight than did controls by the end of the second trimester (5.2 pounds; 95% CI, 0.2 to 10.2; P = 0.04), whereas women with obesity and PCOS and control women had similar weight gain throughout pregnancy. Within normal-weight, overweight, and obese groups, prevalence of pre-eclampsia and gestational diabetes did not differ between the PCOS and control groups, nor was there a difference in birthweight. Preconception body mass index (BMI) was significantly associated with GWG; for every 1-kg/m2 increase in preconception BMI, GWG decreased by 0.62 pounds (95% CI, -0.85 to -0.40; P < 0.001).Conclusions: Women with PCOS who are of normal weight or are overweight before conception experience more GWG than do ovulatory controls. Within normal-weight, overweight, and obese groups, rates of perinatal complications do not significantly differ between women with PCOS and controls. Preconception BMI is the strongest predictor of GWG.

  View details for PubMedID 30085187

• Gestational Weight Gain in Women With Polycystic Ovary Syndrome: A Controlled Study JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Kent, J., Dodson, W. C., Kunselman, A., Pauli, J., Stone, A., Diamond, M. P., Coutifaris, C., Schlaff, W. D., Alvero, R., Casson, P., Christman, G. M., Rosen, R., Hansen, K. R., Robinson, R. D., Baker, V., Usadi, R., Santoro, N., Zhang, H., Eisenberg, E., Legro, R. S., Reprod Med Network 2018; 103 (11): 4315–23

  View details for DOI 10.1210/jc.2017-02764

  View details for Web of Science ID 000456136900042

• Allostatic load, a measure of chronic physiological stress, is associated with pregnancy outcomes, but not fertility, among women with unexplained infertility. Human reproduction (Oxford, England) Barrett, E. S., Vitek, W., Mbowe, O., Thurston, S. W., Legro, R. S., Alvero, R., Baker, V., Bates, G. W., Casson, P., Coutifaris, C., Eisenberg, E., Hansen, K., Krawetz, S., Robinson, R., Rosen, M., Usadi, R., Zhang, H., Santoro, N., Diamond, M. 2018; 33 (9): 1757–66

  Abstract

  STUDY QUESTION: Among infertile women undergoing ovarian stimulation, is allostatic load (AL), a measure of chronic physiological stress, associated with subsequent fertility and pregnancy outcomes?SUMMARY ANSWER: AL at baseline was not associated with conception, spontaneous abortion or live birth, however, it was significantly associated with increased odds of pre-eclampsia and preterm birth among women who had a live birth in the study.WHAT IS KNOWN ALREADY: Several studies have linked AL during pregnancy to adverse outcomes including preterm birth and pre-eclampsia, hypothesizing that it may contribute to well-documented disparities in pregnancy and birth outcomes. However, AL biomarkers change over the course of pregnancy, raising questions as to whether gestational AL assessment is a valid measure of cumulative physiologic stress starting long before pregnancy. To better understand how AL may impact reproductive outcomes, AL measurement in the non-pregnant state (i.e. prior to conception) is needed.STUDY DESIGN, SIZE, DURATION: A secondary data analysis based on data from 836 women who participated in Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), a multi-center, randomized clinical trial of ovarian stimulation conducted from 2011 to 2014.PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovulatory women with unexplained infertility (ages 18-40) were enrolled and at baseline, biological and anthropometric measures were collected. AL scores were calculated as a composite of the following baseline variables determined a priori: BMI, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, dehydroepiandrosterone sulfate, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein and HOMA score. Participants received ovarian stimulation for up to four cycles and if they conceived, were followed throughout pregnancy. We fit multi-variable logistic regression models examining AL (one-tailed and two-tailed) in relation to the following reproductive outcomes: conception, spontaneous abortion, live birth, pre-eclampsia, preterm birth and low birthweight.MAIN RESULTS AND THE ROLE OF CHANCE: Adjusting for covariates, a unit increase in two-tailed AL score was associated with 62% increased odds of pre-eclampsia (OR: 1.62, 95% CI: 1.14, 2.38) 44% increased odds of preterm birth (OR: 1.44, 95% CI: 1.02, 2.08), and 39% increased odds of low birthweight (OR: 1.39, 95% CI: 0.99, 1.97). The relationship between AL and preterm birth was mediated by pre-eclampsia (P = 0.0003). In one-tailed AL analyses, associations were similar, but slightly attenuated. AL was not associated with fertility outcomes (conception, spontaneous abortion, live birth).LIMITATIONS, REASONS FOR CAUTION: Results may not be generalizable to fertile women who conceive naturally or women with other types of infertility. Comparisons to previous, related work are difficult because variables included in AL composite measures vary across studies. AL may be indicative of overall poor health, rather than being specific to chronic physiological stress.WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that chronic physiological stress may not impact success of ovarian stimulation, however, they confirm and extend previous work suggesting that AL is associated with adverse pregnancy outcomes. Physiological dysregulation due to chronic stress has been proposed as a possible mechanism underlying disparities in birth outcomes, which are currently poorly understood. Assessing biomarkers of physiological dysregulation pre-conception or in early pregnancy, may help to identify women at risk of adverse pregnancy outcomes, particularly pre-eclampsia.STUDY FUNDING/COMPETING INTEREST(S): Support for AMIGOS was provided by: U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10HD055925. Support for the current analysis was provided by T32ES007271, R25HD075737, P30ES001247 and P30ES005022. This research was made possible by funding by American Recovery and Reinvestment Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of NICHD, NIEHS or NIH. E.B., W.V., O.M., R.A., M.R., V.B., G.W.B., C.C., E.E., S.K., R.U., P.C, H.Z., N.S. and S.T. have nothing to disclose. R.L. reported serving as a consultant to Abbvie, Bayer, Kindex, Odega, Millendo and Fractyl and serving as a site investigator and receiving grants from Ferring. K.H. reported receiving grants from Roche Diagnostics and Ferring. R.R. reported a grant from AbbVie. M.D. reported being on the Board of Directors of and a stockholder in Advanced Reproductive Care.TRIAL REGISTRATION NUMBER: Clinical Trials.gov number: NCT01044862.

  View details for PubMedID 30085177

• Allostatic load, ameasure of chronic physiological stress, is associated with pregnancy outcomes, but not fertility, among women with unexplained infertility HUMAN REPRODUCTION Barrett, E. S., Vitek, W., Mbowe, O., Thurston, S. W., Legro, R. S., Alvero, R., Baker, V., Bates, G., Casson, P., Coutifaris, C., Eisenberg, E., Hansen, K., Krawetz, S., Robinson, R., Rosen, M., Usadi, R., Zhang, H., Santoro, N., Diamond, M. 2018; 33 (9): 1757–66

  View details for DOI 10.1093/humrep/dey261

  View details for Web of Science ID 000452615200019

• Discordant anti-mullerian hormone (AMH) and follicle stimulating hormone (FSH) among women undergoing in vitro fertilization (IVF): which one is the better predictor for live birth? JOURNAL OF OVARIAN RESEARCH Wang, S., Zhang, Y., Mensah, V., Huber, W. J., Huang, Y., Alvero, R. 2018; 11: 60

  Abstract

  This study sought to clarify the roles of Anti-müllerian hormone (AMH) and follicle stimulating hormone (FSH) in predicting live birth, especially in patients with discordant AMH and FSH. A large IVF data set provided by eIVF®, consisting of 13,964 cycles with AMH, FSH, age, BMI, and birth outcomes were evaluated. Patients were categorized into four groups: Good prognosis group (AMH ≥1 ng/ml; FSH < 10 mIU/ml), Poor prognosis group (AMH < 1 ng/ml; FSH ≥10 mIU/ml), Reassuring AMH group (AMH ≥1 ng/ml; FSH ≥10 mIU/ml), and Reassuring FSH group (AMH < 1 ng/ml; FSH < 10 mIU/ml). The interaction between AMH, FSH, and their impact on live birth rate among these four groups was evaluated using Generalized Additive Mixed Modeling (GAMM).Analysis revealed a nonlinear relationship of AMH and FSH with live birth rate among all ages. Among the four groups, the good prognosis group had the highest live birth rate while the poor prognosis group had the lowest live birth rate (29.3% vs 13.1%, p < 0.005). In the discordant groups, the live birth rate of the reassuring AMH group was significantly higher than the reassuring FSH group (22.8% vs 15.6%, p < 0.005).Although both FSH and AMH are widely use to assess the ovarian reserve in women undergoing evaluation for infertility, AMH appears to be superior to FSH among all age groups. This is particularly important for patients with discordant AMH and FSH where reassuring AMH is a better clinical predictor of cycle success.

  View details for DOI 10.1186/s13048-018-0430-z

  View details for Web of Science ID 000438941300002

  View details for PubMedID 30012195

  View details for PubMedCentralID PMC6048693

• Midluteal Progesterone: A Marker of Treatment Outcomes in Couples With Unexplained Infertility JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Hansen, K. R., Eisenberg, E., Baker, V., Hill, M. J., Chen, S., Talken, S., Diamond, M. P., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P., Christman, G. M., Santoro, N., Zhang, H., Wild, R. A., NICHD Reproductive Med Network 2018; 103 (7): 2743–51

  Abstract

  Adequate luteal phase progesterone exposure is necessary to induce endometrial changes required for a successful pregnancy outcome. The relationship between low midluteal progesterone concentration and the outcome of live birth in ovarian stimulation with intrauterine insemination (OS-IUI) treatments is not defined.To determine the level of midluteal progesterone portending a low chance of live birth after OS-IUI in couples with unexplained infertility.Secondary analyses of data from a prospective, randomized, multicenter clinical trial that determined pregnancy outcomes following OS-IUI with clomiphene citrate, letrozole, or gonadotropins for couples with unexplained infertility.Couples (n = 900) underwent 2376 OS-IUI cycles during the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial.Live birth as it relates to midluteal progesterone level and thresholds below which no live births occur by treatment group.Thresholds for non-live birth cycles were similar for clomiphene (14.4 ng/mL) and letrozole (13.1 ng/mL) yet were lower for gonadotropin (4.3 ng/mL) treatments. A midluteal progesterone level >10th percentile specific for each treatment group independently was associated with greater odds for a live birth in all OS-IUI cycles (adjusted OR: 2.17; 95% CI: 1.05, 4.48).During OS-IUI, a low midluteal progesterone level was associated with a low probability of live birth. Thresholds differed by medication, with the lowest threshold for gonadotropin. Several pathophysiologic mechanisms may account for low progesterone levels. Refinement of the predictive range associated with particular ovarian stimulation medications during treatment of unexplained infertility may improve accuracy.

  View details for PubMedID 29767754

• Coping in Women With Polycystic Ovary Syndrome: Implications for Practitioners JNP-JOURNAL FOR NURSE PRACTITIONERS Carron, R., Kooienga, S., Boyle, D. K., Alvero, R. 2017; 13 (10): 700–707

  View details for DOI 10.1016/j.nurpra.2017.08.004

  View details for Web of Science ID 000414995300021

• Mandating Coverage for Fertility Preservation - A Step in the Right Direction NEW ENGLAND JOURNAL OF MEDICINE Cardozo, E. R., Huber, W. J., Stuckey, A. R., Alvero, R. J. 2017; 377 (17): 1607–9

  View details for DOI 10.1056/NEJMp1709585

  View details for Web of Science ID 000413691900002

  View details for PubMedID 29069561

• Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility. American journal of obstetrics and gynecology Diamond, M. P., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P. A., Christman, G. M., Huang, H., Hansen, K. R., Baker, V., Usadi, R., Seungdamrong, A., Bates, G. W., Rosen, R. M., Schlaff, W., Haisenleder, D., Krawetz, S. A., Barnhart, K., Trussell, J. C., Santoro, N., Eisenberg, E., Zhang, H. 2017

  Abstract

  While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed.The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility.A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale.Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility.Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function.

  View details for DOI 10.1016/j.ajog.2017.04.034

  View details for PubMedID 28455078

• Association of uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination for unexplained infertility FERTILITY AND STERILITY Styer, A. K., Jin, S., Liu, D., Wang, B., Polotsky, A. J., Christianson, M. S., Vitek, W., Engmann, L., Hansen, K., Wild, R., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P., Christman, G. M., Christy, A., Diamond, M. P., Eisenberg, E., Zhang, H., Santoro, N., Natl Inst Child Hlth Human Dev 2017; 107 (3): 756-+

  Abstract

  To investigate the association of non-cavity-distorting uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination (OS-IUI) in couples with unexplained infertility.Secondary analysis from a prospective, randomized, multicenter clinical trial investigating fertility outcomes after OS-IUI.Reproductive Medicine Network clinical sites.Nine hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial.Participants were randomized to one of three arms (clomiphene citrate, letrozole, or gonadotropins), and treatment was continued for up to four cycles or until pregnancy was achieved.Conception (serum hCG increase), clinical pregnancy (fetal cardiac activity), and live birth rates.A total of 102/900 participants (11.3%) had at least one documented fibroid and a normal uterine cavity. Women with fibroids were older, more likely to be African American, had a greater uterine volume, lower serum antimüllerian hormone levels, and fewer antral follicles than women without fibroids. In conception cycles, clinical pregnancy rates were significantly lower in participants with fibroids than in those without uterine fibroids. Pregnancy loss before 12 weeks was more likely in African American women with fibroids compared with non-African American women with fibroids. There was no difference in conception and live birth rates in subjects with and without fibroids.No differences were observed in conception and live birth rates in women with non-cavity-distorting fibroids and those without fibroids. These findings provide reassurance that pregnancy success is not impacted in couples with non-cavity-distorting fibroids undergoing OS-IUI for unexplained infertility.NCT01044862.

  View details for DOI 10.1016/.fertnstert.2016.12.012

  View details for Web of Science ID 000397985500038

  View details for PubMedID 28089575

  View details for PubMedCentralID PMC5472203

• Fertility-related quality of life from two RCT cohorts with infertility: unexplained infertility and polycystic ovary syndrome HUMAN REPRODUCTION Santoro, N., Eisenberg, E., Trussell, J. C., Craig, L. B., Gracia, C., Huang, H., Alvero, R., Casson, P., Christman, G., Coutifaris, C., Diamond, M., Jin, S., Legro, R. S., Robinson, R. D., Schlaff, W. D., Zhang, H., Reprod Med Network Investigators 2016; 31 (10): 2268–79

  Abstract

  Does fertility-related quality of life (FertiQOL) differ by infertility diagnosis between women with polycystic ovary syndrome (PCOS) and their partners, compared with couples with unexplained infertility (UI)?Women with PCOS report lower QOL than those with UI, whereas males with UI report lower QOL than males with PCOS partners.The fertility-specific QOL survey, FertiQOL, has been used to examine fertility-related QOL in a number of worldwide cohorts. Few data have addressed fertility-related QOL as a function of infertility diagnosis. Overall, men report better QOL than women with infertility, and there is variation in FertiQOL scores across different samples from different countries.This was a prospective, cohort study derived from two concurrent, randomized clinical trials, and designed to examine QOL in infertile females with PCOS and UI at the time of enrollment compared with each other and their male partners; to compare concordance FertiQOL scores in this study across other worldwide cohorts; and to determine if baseline FertiQOL was associated with pregnancy outcome.Women with PCOS and their partners (n = 733 and n = 641, respectively), and couples with UI (n = 865 women and 849 men) completed a validated fertility-specific QOL survey (FertiQOL) at the time of the study screening visit. PCOS women were randomized to either clomiphene citrate or letrozole treatment; couples with UI were randomized to clomiphene citrate, letrozole or gonadotrophin plus IUI. FertiQOL results were compiled by diagnosis (PCOS or UI) and compared by diagnosis and sex using Wilcoxon Rank-Sum testing. Relationships between baseline FertiQOL and pregnancy outcomes were examined using logistic regression. Multivariable models were performed to assess the association between FertiQOL scores and key participant characteristics.Women with PCOS had lower total FertiQOL scores (72.3 ± 14.8) than those with UI (77.1 ± 12.8; P < 0.001); this was true for each domain (except Relational). These differences were largely explained by variation in BMI, hirsutism, household income and age. Women had lower overall FertiQOL scores than their male partners. Males with PCOS partners had higher scores than males with UI (84.9 ± 10.2 versus 83.3 ± 10.8; P = 0.003). Scores were not consistently associated with conception or pregnancy outcome.The use of multiple tests of association may have resulted in spurious statistically significant findings. Inherent sociodemographic differences between women with PCOS and those with UI largely account for the lower QOL in women with PCOS. Our study was unable to assess if changes in QOL affected pregnancy outcome as FertiQOL data were collected prior to treatment. Finally, the participants for both studies represent their local communities, but are not a population-based sample and thus firm conclusions about how representative these couples are to the general population must be made with caution.Women with PCOS with elevated BMI and hirsutism scores and with lower socioeconomic status may require more, targeted psychosocial support than those with other diagnoses. Possible attribution of infertility to the male partner appears to result in a lower QOL. There appears to be substantial national variation in FertiQOL scores, with US-based cohorts reporting overall higher QOL.This work was supported by National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD39005 (to M.D.), U10 HD38992 (to R.S.L.), (to C.C.), U10 HD38998 (to R.A.), U10 HD055942 (to R.D.R.), HD055944 (to P.C.), U10 HD055936 (to G.C.), U10HD055925 (to H.Z.); and U10 U54-HD29834 (to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core of the Specialized Cooperative Centers Program in Reproduction and Infertility Research). Most importantly, this research was made possible by the funding by American Recovery and Reinvestment Act. N.S., E.E., J.C.T., C.G., H.H., R.A., P.C., G.C., C.C., M.D., S.J., W.D.S. and H.Z. report no conflicts of interests/disclosures. L.B.C. reports research support from Ferring Pharmaceuticals and Roche Diagnostics; R.S.L. reports receipt of consulting fees from AstraZeneca, Euroscreen, Sprout Pharmaceuticals, Taken, Kindex, Clarus and Bayer, Inc., and research support from AstraZeneca and Ferring Pharmaceuticals. R.D.R. reports research support from AbbVie.Pregnancy in Polycystic Ovary Syndrome II (PPCOS II), NCT00719186; Assessment of Multiple Intrauterine Gestations in Ovulation Stimulation (AMIGOS) NCT01044862, clinicaltrials.gov.PPCOS II 17 July 2008; AMIGOS 7 January 2010.PPCOS II 19 February 2009; AMIGOS 2 August 2010.

  View details for DOI 10.1093/humrep/dew175

  View details for Web of Science ID 000386087000014

  View details for PubMedID 27402910

  View details for PubMedCentralID PMC5027926

• Predictors of pregnancy and live-birth in couples with unexplained infertility after ovarian stimulation intrauterine insemination FERTILITY AND STERILITY Hansen, K. R., He, A. W., Styer, A. K., Wild, R. A., Butts, S., Engmann, L., Diamond, M. P., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P., Christman, G. M., Huang, H., Santoro, N., Eisenberg, E., Zhang, H., Eunice Kennedy Shriver Natl Inst 2016; 105 (6): 1575–U262

  Abstract

  To identify baseline characteristics of couples that are likely to predict conception, clinical pregnancy, and live birth after up to four cycles of ovarian stimulation with IUI in couples with unexplained infertility.Secondary analyses of data from a prospective, randomized, multicenter clinical trial investigating pregnancy, live birth, and multiple pregnancy rates after ovarian stimulation-IUI with clomiphene citrate, letrozole, or gonadotropins.Outpatient clinical units.Nine-hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial.As part of the clinical trial, treatment was randomized equally to one of three arms and continued for up to four cycles or until pregnancy was achieved.Conception, clinical pregnancy, and live-birth rates.In a multivariable logistic regression analysis, after adjustment for other covariates, age, waist circumference, income level, duration of infertility, and a history of prior pregnancy loss were significantly associated with at least one pregnancy outcome. Other baseline demographic and lifestyle characteristics including smoking, alcohol use, and serum levels of antimüllerian hormone were not significantly associated with pregnancy outcomes.While age and duration of infertility were significant predictors of all pregnancy outcomes, many other baseline characteristics were not. The identification of level of income as a significant predictor of outcomes independent of race and education may reflect differences in the underlying etiologies of unexplained infertility or could reveal disparities in access to fertility and/or obstetrical care.NCT01044862.

  View details for DOI 10.1016/j.fertnstert.2016.02.020

  View details for Web of Science ID 000377290900032

  View details for PubMedID 26949110

  View details for PubMedCentralID PMC4893990

• Considerations for management of interstitial ectopic pregnancies: two case reports. Journal of medical case reports Grindler, N. M., Ng, J., Tocce, K., Alvero, R. 2016; 10 (1): 106

  Abstract

  BACKGROUND: Conventional treatment of interstitial pregnancies includes systemic methotrexate, direct methotrexate injection, wedge resection, or hysterectomy. We present two cases of interstitial pregnancies that were successfully managed by different minimally invasive surgical techniques. We also report the novel use of hysteroscopic urologic stone retrieval forceps in the transvaginal removal of persistent products of conception after systemic methotrexate for an interstitial pregnancy.CASE PRESENTATION: Case 1 was a 28-year-old gravida 1 white woman at 8 weeks gestation; she was diagnosed with a left interstitial pregnancy. After laparoscopic confirmation of the interstitial pregnancy, successful ultrasound-guided suction dilation and curettage was performed. Case 2 was a 33-year-old gravida 3 para 1021 (one term pregnancy, no preterm pregnancies, one ectopic pregnancy and one spontaneous miscarriage, and one living child) Hispanic woman with persistent products of conception after systemic methotrexate for a left interstitial pregnancy. She underwent hysteroscopic-guided removal of the persistent products of conception, which was possible due to novel use of urologic stone retrieval forceps.CONCLUSIONS: Successful minimally invasive treatment of interstitial pregnancies may be possible in certain cases. Collaboration between different specialties continues to be important for improving minimally invasive options.

  View details for DOI 10.1186/s13256-016-0892-9

  View details for PubMedID 27118381

• Chlamydia trachomatis immunoglobulin G3 seropositivity is a predictor of reproductive outcomes in infertile women with patent fallopian tubes. Fertility and sterility Steiner, A. Z., Diamond, M. P., Legro, R. S., Schlaff, W. D., Barnhart, K. T., Casson, P. R., Christman, G. M., Alvero, R., Hansen, K. R., Geisler, W. M., Thomas, T., Santoro, N., Zhang, H., Eisenberg, E. 2015; 104 (6): 1522-6

  Abstract

  To determine if Chlamydia trachomatis (C. trachomatis) seropositivity, as detected by the C. trachomatis elementary body (EB)-based enzyme-linked immunosorbent assay [EB ELISA] predicts pregnancy and pregnancy outcome among infertile women with documented tubal patency.Cohort study.Outpatient clinics.In all, 1,250 infertile women with documented tubal patency enrolled in 1 of 2 randomized controlled trials: Pregnancy in Polycystic Ovary Syndrome II; and the Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation.Sera were analyzed for anti-C. trachomatis immunoglobulin G (IgG)1 and IgG3 antibodies, using a research C. trachomatis EB ELISA. The optical density (OD)405 readings of ≥ 0.35 and ≥ 0.1 were considered positive for IgG1 and IgG3, respectively.Primary outcomes included pregnancy, live birth, and ectopic pregnancy. Log-linear regression was used to determine the relative risk after adjusting for age, race, treatment medication, smoking status, and current alcohol use.A total of 243 (19%) women were seropositive for anti-C. trachomatis IgG3. They tended to be nonwhite and smokers. Anti-C. trachomatis IgG3 seropositive women were significantly less likely to conceive (risk ratio [RR] 0.65, 95% confidence interval [CI] 0.52-0.83) or to have a live birth (RR 0.59, 95% CI 0.43-0.80); these associations were weakened after adjusting for number of hysterosalpingography-documented patent tubes (RR 0.73, 95% CI 0.56-0.97) and (RR 0.73, 95% CI 0.50-1.04), respectively. Anti-C. trachomatis IgG3 seropositive women who conceived had a ×2.7 risk (95% CI 1.40-5.34) of ectopic pregnancy.Even in the presence of tubal patency, anti-C. trachomatis IgG3 seropositivity is associated with a lower likelihood of pregnancy. Anti-C. trachomatis IgG3 seropositive women have as high as 3 times the risk of ectopic pregnancy.PPCOSII: NCT00719186 and AMIGOS: NCT01044862.

  View details for DOI 10.1016/j.fertnstert.2015.08.022

  View details for PubMedID 26413816

  View details for PubMedCentralID PMC4663111

• Recruitment strategies in two reproductive medicine network infertility trials. Contemporary clinical trials Usadi, R. S., Diamond, M. P., Legro, R. S., Schlaff, W. D., Hansen, K. R., Casson, P., Christman, G., Wright Bates, G., Baker, V., Seungdamrong, A., Rosen, M. P., Lucidi, S., Thomas, T., Huang, H., Santoro, N., Eisenberg, E., Zhang, H., Alvero, R. 2015; 45 (Pt B): 196-200

  Abstract

  Recruitment of individuals into clinical trials is a critical step in completing studies. Reports examining the effectiveness of different recruitment strategies, and specifically in infertile couples, are limited.We investigated recruitment methods used in two NIH sponsored trials, Pregnancy in Polycystic Ovary Syndrome (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), and examined which strategies yielded the greatest number of participants completing the trials.3683 couples were eligible for screening. 1650 participants were randomized and 1339 completed the trials. 750 women were randomized in PPCOS II; 212 of the participants who completed the trial were referred by physicians. Participants recruited from radio ads (84/750) and the internet (81/750) resulted in similar rates of trial completion in PPCOS II. 900 participants were randomized in AMIGOS. 440 participants who completed the trial were referred to the study by physicians. The next most successful method in AMIGOS was the use of the internet, achieving 78 completed participants. Radio ads proved the most successful strategy in both trials for participants who earned <$50,000 annually. Radio ads were most successful in enrolling white patients in PPCOS II and black patients in AMIGOS. Seven ancillary Clinical Research Scientist Training (CREST) sites enrolled 324 of the participants who completed the trials.Physician referral was the most successful recruitment strategy. Radio ads and the internet were the next most successful strategies, particularly for women of limited income. Ancillary clinical sites were important for overall recruitment.

  View details for DOI 10.1016/j.cct.2015.09.010

  View details for PubMedID 26386293

  View details for PubMedCentralID PMC4766588

• Recruitment strategies in two reproductive medicine network infertility trials CONTEMPORARY CLINICAL TRIALS Usadi, R. S., Diamond, M. P., Legro, R. S., Schlaff, W. D., Hansen, K. R., Casson, P., Christman, G., Bates, G. W., Baker, V., Seungdamrong, A., Rosen, M. P., Lucidi, S., Thomas, T., Huang, H., Santoro, N., Eisenberg, E., Zhang, H., Alvero, R. 2015; 45: 196-200

  Abstract

  Recruitment of individuals into clinical trials is a critical step in completing studies. Reports examining the effectiveness of different recruitment strategies, and specifically in infertile couples, are limited.We investigated recruitment methods used in two NIH sponsored trials, Pregnancy in Polycystic Ovary Syndrome (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), and examined which strategies yielded the greatest number of participants completing the trials.3683 couples were eligible for screening. 1650 participants were randomized and 1339 completed the trials. 750 women were randomized in PPCOS II; 212 of the participants who completed the trial were referred by physicians. Participants recruited from radio ads (84/750) and the internet (81/750) resulted in similar rates of trial completion in PPCOS II. 900 participants were randomized in AMIGOS. 440 participants who completed the trial were referred to the study by physicians. The next most successful method in AMIGOS was the use of the internet, achieving 78 completed participants. Radio ads proved the most successful strategy in both trials for participants who earned <$50,000 annually. Radio ads were most successful in enrolling white patients in PPCOS II and black patients in AMIGOS. Seven ancillary Clinical Research Scientist Training (CREST) sites enrolled 324 of the participants who completed the trials.Physician referral was the most successful recruitment strategy. Radio ads and the internet were the next most successful strategies, particularly for women of limited income. Ancillary clinical sites were important for overall recruitment.

  View details for DOI 10.1016/j.cct.2015.09.010

  View details for Web of Science ID 000367755200009

  View details for PubMedCentralID PMC4766588

• Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility NEW ENGLAND JOURNAL OF MEDICINE Diamond, M. P., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P., Christman, G. M., Ager, J., Huang, H., Hansen, K. R., Baker, V., Usadi, R., Seungdamrong, A., Bates, G. W., Rosen, R. M., HAISENLEDER, D., Krawetz, S. A., Barnhart, K., Trussell, J. C., Ohl, D., Jin, Y., Santoro, N., Eisenberg, E., Zhang, H. 2015; 373 (13): 1230-1240

  Abstract

  The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates.We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies.After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications.In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.).

  View details for DOI 10.1056/NEJMoa1414827

  View details for PubMedID 26398071

• Identification and replication of prediction models for ovulation, pregnancy and live birth in infertile women with polycystic ovary syndrome. Human reproduction Kuang, H., Jin, S., Hansen, K. R., Diamond, M. P., Coutifaris, C., Casson, P., Christman, G., Alvero, R., Huang, H., Bates, G. W., Usadi, R., Lucidi, S., Baker, V., Santoro, N., Eisenberg, E., Legro, R. S., Zhang, H. 2015; 30 (9): 2222-2233

  Abstract

  Can we build and validate predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS)?We were able to develop and validate a predictive model for pregnancy outcomes in women with PCOS using simple clinical and biochemical criteria particularly duration of attempting conception, which was the most consistent predictor among all considered factors for pregnancy outcomes.Predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome have been reported, but such models require validation.This is a secondary analysis of the data from the Pregnancy in Polycystic Ovary Syndrome I and II (PPCOS-I and -II) trials. Both trials were double-blind, randomized clinical trials that included 626 and 750 infertile women with PCOS, respectively. PPCOS-I participants were randomized to either clomiphene citrate (CC), metformin, or their combination, and PPCOS-II participants to either letrozole or CC for up to five treatment cycles.Linear logistic regression models were fitted using treatment, BMI, and other published variables as predictors of ovulation, conception, clinical pregnancy, and live birth as the outcome one at a time. We first evaluated previously reported significant predictors, and then constructed new prediction models. Receiver operating characteristic (ROC) curves were constructed and the area under the curves (AUCs) was calculated to compare performance using different models and data. Chi-square tests were used to examine the goodness-of-fit and prediction power of logistic regression model.Predictive factors were similar between PPCOS-I and II, but the two participant samples differed statistically significantly but the differences were clinically minor on key baseline characteristics and hormone levels. Women in PPCOS-II had an overall more severe PCOS phenotype than women in PPCOS-I. The clinically minor but statistically significant differences may be due to the large sample sizes. Younger age, lower baseline free androgen index and insulin, shorter duration of attempting conception, and higher baseline sex hormone-binding globulin significantly predicted at least one pregnancy outcome. The ROC curves (with AUCs of 0.66-0.76) and calibration plots and chi-square tests indicated stable predictive power of the identified variables (P-values ≥0.07 for all goodness-of-fit and validation tests).This is a secondary analysis. Although our primary objective was to confirm previously reported results and identify new predictors of ovulation and pregnancy outcomes among PPCOS-II participants, our approach is exploratory and warrants further replication.We have largely confirmed the predictors that were identified in the PPCOS-I trial. However, we have also revealed new predictors, particularly the role of smoking. While a history of ever smoking was not a significant predictor for live birth, a closer look at current, quit, and never smoking revealed that current smoking was a significant risk factor.The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD27049, U10 HD38992, U10HD055925, U10 HD39005, U10 HD33172, U10 HD38998, U10 HD055936, U10 HD055942, and U10 HD055944; and U54-HD29834. Heilongjiang University of Chinese Medicine Grants 051277 and B201005. R.S.L. reports receiving consulting fees from Euroscreen, AstraZeneca, Clarus Therapeutics, and Takeda, and grant support from Ferring, Astra Zeneca, and Toba. K.R.H. reports receiving grant support from Roche Diagnostics and Ferring Pharmascience. G.C. reports receiving Honorarium and grant support from Abbvie Pharmaceuticals and Bayer Pharmaceuticals. M.P.D. holds equity from Advanced Reproductive Care Inc. and DS Biotech, receives fees from Advanced Reproductive Care Inc., Actamax, Auxogyn, ZSX Medical, Halt Medical, and Neomed, and receives grant support from Boehringer-Ingelheim, Abbott, and BioSante, Ferring Pharmaceuticals, and EMD Serono. H.Z. receives research support from the Chinese 1000-scholar plan. Others report no disclosures other than NIH grant support.PPCOS-I and -II were respectively registered at Clinicaltrials.gov: NCT00719186 and NCT00719186.

  View details for DOI 10.1093/humrep/dev182

  View details for PubMedID 26202922

  View details for PubMedCentralID PMC4542721

• Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations NATURE COMMUNICATIONS Hayes, M., Urbanek, M., Ehrmann, D. A., Armstrong, L. L., Lee, J., Sisk, R., Karaderi, T., Barber, T. M., McCarthy, M. I., Franks, S., Lindgren, C. M., Welt, C. K., Diamanti-Kandarakis, E., Panidis, D., Goodarzi, M. O., Azziz, R., Zhang, Y., James, R. G., Olivier, M., Kissebah, A. H., Stener-Victorin, E., Legro, R. S., Dunaif, A., Reprod Med Network 2015; 6: 7502

  Abstract

  Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case-control meta-analysis, two novel loci mapping to chr 8p23.1 [Corrected] and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis.

  View details for DOI 10.1038/ncomms8502

  View details for Web of Science ID 000360339100001

  View details for PubMedID 26284813

  View details for PubMedCentralID PMC4557132

• Assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial: baseline characteristics FERTILITY AND STERILITY Diamond, M. P., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P., Christman, G. M., Ager, J., Huang, H., Hansen, K. R., Baker, V., Usadi, R., Seungdamrong, A., Bates, G. W., Rosen, R. M., Haisonleder, D., Krawetz, S. A., Barnhart, K., Trussell, J. C., Jin, Y., Santoro, N., Eisenberg, E., Zhang, H. 2015; 103 (4): 962-U143

  Abstract

  To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications.Randomized, prospective clinical trial.Multicenter university-based clinical practices.A total of 900 couples with unexplained infertility.Collection of baseline demographics, blood samples, and ultrasonographic assessments.Demographic, laboratory, imaging, and survey characteristics.Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners.The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment.NCT 01044862.

  View details for DOI 10.1016/j.fertnstert.2014.12.130

  View details for Web of Science ID 000352110400024

  View details for PubMedID 25707331

• Keeping clinicians in research: the Clinical Research/Reproductive Scientist Training Program (CREST) strategy, 2006-2012. Fertility and sterility Usadi, R. S., Alvero, R., Armstrong, A. Y., Rebar, R. W., DeCherney, A. H., Maddox, Y. T. 2014; 102 (6): 1542-4

  View details for DOI 10.1016/j.fertnstert.2014.09.002

  View details for PubMedID 25439798

• Para mejor informar: using technology for medical education in the Latino community. Fertility and sterility Alvero, R. 2014; 102 (5): 1256-7

  View details for DOI 10.1016/j.fertnstert.2014.08.024

  View details for PubMedID 25241374

• Multivariate analysis of factors affecting probability of pregnancy and live birth with in vitro fertilization: an analysis of the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System FERTILITY AND STERILITY Baker, V. L., Luke, B., Brown, M. B., Alvero, R., Frattarelli, J. L., Usadi, R., Grainger, D. A., Armstrong, A. Y. 2010; 94 (4): 1410-1416

  Abstract

  To evaluate factors predictive of clinical pregnancy and of pregnancy loss from assisted reproductive technology (ART) using data from the Society for Assisted Reproductive Technology database for 2004-2006.Retrospective cohort.Clinic-based data.The study population included 225,889 fresh embryo transfer cycles using autologous oocytes and partner semen.None.Clinical intrauterine gestation (presence of gestational sac) and live birth (>or=22 weeks gestation and >or=300 g birth weight).Increasing maternal age was significantly associated with a reduced odds of conception and increased fetal loss until 19 weeks gestation, but not with later pregnancy loss. Intracytoplasmic sperm injection (ICSI), assisted hatching, and increasing number of embryos transferred had significant positive effects on the odds of conception and pregnancy continuation through the first trimester, but did not affect the risk of later loss. Blacks, Asians, and Hispanics had significantly lower odds of clinical pregnancy compared with whites. Also compared with whites, Hispanics and Asians had a significantly greater risk of pregnancy loss in the second and third trimesters, and blacks had a significantly greater risk of pregnancy loss in all trimesters.Certain demographic and ART treatment parameters influenced chance of conception and early pregnancy loss, whereas black race and Hispanic ethnicity were also significantly associated with late pregnancy loss in ART-conceived pregnancies.

  View details for DOI 10.1016/j.fertnstert.2009.07.986

  View details for Web of Science ID 000281674600041

  View details for PubMedID 19740463

• Economics may not explain Hispanic underutilization of assisted reproductive technology services FERTILITY AND STERILITY Feinberg, E. C., Larsen, F. W., Wah, R. M., Alvero, R. J., Armstrong, A. Y. 2007; 88 (5): 1439–41

  Abstract

  In a lower cost, equal-access-to-care setting, Hispanic use of assisted reproductive technology was less than half of what would have been expected based on patient demographics. Despite this use disparity, there were no significant differences between Hispanic and Caucasian women with regard to infertility diagnoses, assisted reproductive technology cycle parameters, clinical pregnancy rates, live birth rates, spontaneous abortion rates, and implantation rates.

  View details for DOI 10.1016/j.fertnstert.2007.01.031

  View details for Web of Science ID 000250981300027

  View details for PubMedID 17561005

• Too little time to teach? Medical student education and the resident work-hour restriction. Military medicine Zahn, C. M., Dunlow, S. G., Alvero, R., Parker, J. D., Nace, C., Armstrong, A. Y. 2007; 172 (10): 1053-7

  Abstract

  The purpose of this study was to examine the impact of the resident duty-hour restriction on medical student education through a survey of faculty, residents, and interns, with interns providing experience as students relative to implementation of work-hour restrictions.A survey was performed at two (one military and one civilian) obstetrics and gynecology residency programs. Additional surveys were obtained from an Association of Professors of Gynecology and Obstetrics workshop, which included military and nonmilitary attendees.The majority of faculty reported spending 5 to 10 hours per week in medical education before and after implementation of the work-hour restriction. Residents reported less time teaching students after work-hour restrictions were instituted. Nearly all interns, responding about their clinical clerkship experience as students, believed their educational experience would have been improved if residents were more involved in teaching.This pilot study suggests residents are less involved in medical student education following implementation of the duty-hour restrictions.

  View details for DOI 10.7205/milmed.172.10.1053

  View details for PubMedID 17985765

• Resident job satisfaction: One year of duty hours Lund, K. J., Teal, S. B., Alvero, R. MOSBY, INC. 2005: 1823–26

  Abstract

  This study was undertaken to assess job satisfaction and quality of life aspects among residents in obstetrics/gynecology before and after the implementation of duty-hour requirements.We administered a survey to residents before and after duty-hour restrictions, addressing satisfaction with residency training, quality of life, and predictions/impressions of the effect of reduced work hours.Satisfaction with overall residency training as a discrete survey item did not change; however, the composite score from all responses to specific items increased. Several specific clinical and academic items garnered higher satisfaction scores in 2004. Residents reported less-than-anticipated increases in healthiness of their lifestyle and a decrease in interest in teaching.This is a prospective assessment of the effect of duty-hour requirements, improvements in residents' perception of their time and ability to study and pursue research and in clinical areas are encouraging. The perception that there is less interest in teaching is of concern.

  View details for DOI 10.1016/j.ajog.2005.07.079

  View details for Web of Science ID 000233122100046

  View details for PubMedID 16260242

• Resident job satisfaction: Will 80 hours make a difference? Lund, K. J., Alvero, R., Teal, S. B. MOSBY, INC. 2004: 1805–10

  Abstract

  This study was undertaken to assess job satisfaction and quality of life among obstetrics and gynecology residents before the 80-hour work week.We administered a job satisfaction survey to residents before July 1, 2003, assessing satisfaction with residency training, indicators of current quality of life, and predictions for the effect of reduced work hours.Residents were satisfied with training, with important outliers, including leisure time, ability to pursue educational reading, and surgical experience. We created job satisfaction facets that were generally reliable constructs and valid predictors for overall residency satisfaction. Residents predict more free time and a healthier lifestyle under the new requirements, but do not anticipate using additional time to study or teach.Job satisfaction facets for residents are proposed here and may be refined through further study. Lower scores for surgical experience are of concern in light of decreasing work hours. Educators must monitor self-directed learning efforts under new work hours.

  View details for DOI 10.1016/j.ajog.2004.07.072

  View details for Web of Science ID 000225337500053

  View details for PubMedID 15547569

• Assessment of resident competency in the performance of sonohysterography: Does the level of training impact the accuracy? AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Parker, J. D., Alvero, R. J., Luterzo, J., Segars, J. H., Armstrong, A. Y. 2004; 191 (2): 582–86

  Abstract

  The objective of this study was to examine the true-positive rates by level of training of the operator and to determine whether the accuracy of the procedure differed by the level of education after formalized training.This was a retrospective analysis. The records of patients who underwent surgery for the indication of an abnormal saline sonohysterography were reviewed from January 2001 to April 2003 (n=73 patients). The nature of the saline sonohysterography abnormality, the intraoperative findings, and the level of training of the provider were recorded. Findings at saline sonohysterography were compared with findings at hysteroscopy or surgery. Statistical significance was determined by chi(2) test.The overall true-positive rate was 86.3% (63/73 patients). The true-positive rates for nurse practitioners, second- and fourth-year residents, and fellows were 84%, 80%, 90%, and 89%, respectively. There was no significant difference among providers (P=.96).The true-positive rates for saline hysterography were comparable among different provider levels.

  View details for DOI 10.1016/j.ajog.2004.03.011

  View details for Web of Science ID 000203976500031

  View details for PubMedID 15343241

• Assisted reproductive technologies: Toward improving implantation rates and reducing high-order multiple gestations OBSTETRICAL & GYNECOLOGICAL SURVEY Alvero, R. 2002; 57 (8): 519–29

  Abstract

  Despite striking progress in reproductive medicine over the past quarter century, the number of high-order multiple gestations are unacceptably high, largely as a result of the drive to maintain pregnancy rates in a competitive range. Morphologic criteria are currently used to define the reproductive competence of individual embryos but are imperfect predictors of implantation potential. Current and potential strategies to improve the selection of embryos are described. By the use of several of these approaches, it is hoped that the overall number of embryos that are transferred will be reduced, thereby also reducing the multiple gestation rate.

  View details for DOI 10.1097/00006254-200208000-00022

  View details for Web of Science ID 000177444600002

  View details for PubMedID 12187151

• The morphology of human pronuclear embryos is positively related to blastocyst development and implantation HUMAN REPRODUCTION Scott, L., Alvero, R., Leondires, M., Miller, B. 2000; 15 (11): 2394–2403

  Abstract

  Human embryos are selected for transfer using morphology at the cleaving and blastocyst stages. Zygote morphology has been related to implantation and pregnancy. The aim of this study was to relate pronuclear morphology to blastocyst development. Zygotes were scored according to distribution and size of nucleoli within each nucleus. Zygotes displaying equality between the nuclei had 49.5% blastocyst formation and those with unequal sizes, numbers or distribution of nucleoli had 28% blastocyst formation. Cleaving embryos that were selected initially by zygote morphology and secondarily by morphology on day 3 had increased implantation (IR) and pregnancy rates (PR; 31 and 57%), compared with those selected by morphology alone (19 and 33% respectively; P: < 0.01). There was a significant difference between zygote-scored and non-scored cycles on day 3 (PR: 57 versus 33%; IR: 31 versus 19%) and on day 5 (PR: 73 versus 58%; IR; 52 versus 39%). Zygote scoring can maintain pregnancy rates for both day 3 and day 5 transfers, increase implantation rates and reduce the numbers of embryos required to achieve a pregnancy.

  View details for DOI 10.1093/humrep/15.11.2394

  View details for Web of Science ID 000165218200027

  View details for PubMedID 11056141

• Effects of fasting on neuroendocrine function and follicle development in lean women JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Alvero, R., Kimzey, L., Sebring, N., Reynolds, J., Loughran, M., Nieman, L., Olson, B. R. 1998; 83 (1): 76–80

  Abstract

  A 72-h fast in normal weight women during the follicular phase results in transient alterations in neuroendocrine function, but follicle development and follicular phase length remain unaltered. In this study we evaluated neuroendocrine and ovulatory function in lean women (body fat, < or = 20%) undergoing a similar 72-h fast. Compared to fed controls, fasted lean women experienced significant weight loss, blunting of the diurnal variation of cortisol, suppression of the nocturnal TSH rise, and a decrease in T3 levels after a 72-h fast. In contrast to similarly fasted, normal weight women, lean women have significantly higher evening cortisol levels and do not exhibit a normal nocturnal TSH rise after the fast. Lean fasted women exhibited a 19% decrease in the number of LH pulses over 24 h compared to fed women (12.9 +/- 1.3 vs. 16.0 +/- 1.9; P < 0.05). Fasting did not result in significant differences in mean LH, LH amplitude, LH area under the curve, and mean FSH levels in these lean women. Of the seven fasted cycles, two were anovulatory. In the five women studied in fed and fasted cycles, one had interrupted lead follicle development with anovulation, and four had significant lengthening of the follicular phase compared to those during their fed cycles (14.4 +/- 1.2 vs. 13.2 +/- 1.0 days; P = 0.01). The clinical observations made in this small sample of lean women showing more profound changes in neuroendocrine function, anovulation, and lengthened follicular phase after fasting suggest that lean women may be more vulnerable to fasting stress than normal weight women.

  View details for DOI 10.1210/jc.83.1.76

  View details for Web of Science ID 000071270600014

  View details for PubMedID 9435419