Steven Nakajima, M.D.

All Publications

• Corrigendum. First PGT-A using human in vivo blastocysts recovered by uterine lavage: comparison with matched IVF embryo controls. Human reproduction (Oxford, England) Munne, S., Nakajima, S. T., Najmabadi, S., Sauer, M. V., Angle, M. J., Rivas, J. L., Mendieta, L. V., Macaso, T. M., Sawarkar, S., Nadal, A., Choudhary, K., Nezhat, C., Carson, S. A., Buster, J. E. 2021

  View details for DOI 10.1093/humrep/deab097

  View details for PubMedID 33904920

• HUMAN UTERINE LAVAGE: EMBRYO SAFETY AND FIRST LIVE BIRTHS FROM IN VIVO CONCEIVED GENETICALLY SCREENED BLASTOCYSTS. Najmabadi, S., Rivas, J. L., Angle, M., Cohen, J., Nadal, A., Bastu, E., Munne, S., Carson, S., Buster, J. E., Nakajima, S. T. ELSEVIER SCIENCE INC. 2020: E165

  View details for Web of Science ID 000579355300404

• PRE-IMPLANTATION GENETIC TESTING (PGT-A) USING FAST-SEQS NGS OF IN VIVO CONCEIVED BLASTOCYSTS RECOVERED BY UTERINE LAVAGE. Alouf, C. A., Najmabadi, S., Nakajima, S. T., Buster, J. E., Faulkner, N. ELSEVIER SCIENCE INC. 2019: E238–E239

  View details for DOI 10.1016/j.fertnstert.2019.07.1368

  View details for Web of Science ID 000487821302092

• EXOGENOUS GONDOTROPIN USE NOT ASSOCIATED WITH INCREASE IN ANEUPLOIDY OF IN VIVO RECOVERED BLASTOCYSTS. Nakajima, S. T., Najmabadi, S., Munne, S., Nadal, A., Choudhary, K., Buster, J. E. ELSEVIER SCIENCE INC. 2019: E135

  View details for DOI 10.1016/j.fertnstert.2019.07.472

  View details for Web of Science ID 000487821301095

• First PGT-A using human in vivo blastocysts recovered by uterine lavage: comparison with matched IVF embryo controls†. Human reproduction (Oxford, England) Munné, S. n., Nakajima, S. T., Najmabadi, S. n., Sauer, M. V., Angle, M. J., Rivas, J. L., Mendieta, L. V., Macaso, T. M., Sawarkar, S. n., Nadal, A. n., Choudhary, K. n., Nezhat, C. n., Carson, S. A., Buster, J. E. 2019

  Abstract

  After controlled ovarian stimulation (COS) and IUI, is it clinically feasible to recover in vivo conceived and matured human blastocysts by uterine lavage from fertile women for preimplantation genetic testing for aneuploidy (PGT-A) and compare their PGT-A and Gardner scale morphology scores with paired blastocysts from IVF control cycles?In a consecutive series of 134 COS cycles using gonadotrophin stimulation followed by IUI, uterine lavage recovered 136 embryos in 42% (56/134) of study cycles, with comparable in vivo and in vitro euploidy rates but better morphology in in vivo embryos.In vivo developed embryos studied in animal models possess different characteristics compared to in vitro developed embryos of similar species. Such comparative studies between in vivo and in vitro human embryos have not been reported owing to lack of a reliable method to recover human embryos.We performed a single-site, prospective controlled trial in women (n = 81) to evaluate the safety, efficacy and feasibility of a novel uterine lavage catheter and fluid recovery device. All lavages were performed in a private facility with a specialized fertility unit, from August 2017 to June 2018. Subjects were followed for 30 days post-lavage to monitor for clinical outcomes and delayed complications. In 20 lavage subjects, a single IVF cycle (control group) with the same ovarian stimulation protocol was performed for a comparison of in vivo to in vitro blastocysts.Women were stimulated with gonadotrophins for COS. The ovulation trigger was given when there were at least two dominant follicles ≥18 mm, followed by IUI of sperm. Uterine lavage occurred 4-6 days after the IUI. A subset of 20 women had a lavage cycle procedure followed by an IVF cycle (control IVF group). Recovered embryos were characterized morphologically, underwent trophectoderm (TE) biopsy, vitrified and stored in liquid nitrogen. Biopsies were analyzed using the next-generation sequencing technique. After lavage, GnRH antagonist injections were administered to induce menstruation.A total of 134 lavage cycles were performed in 81 women. Uterine lavage recovered 136 embryos in 56 (42%) cycles. At the time of cryopreservation, there were 40 (30%) multi-cell embryos and 96 (70%) blastocysts. Blastocysts were of good quality, with 74% (70/95) being Gardener grade 3BB or higher grade. Lavage blastocysts had significantly higher morphology scores than the control IVF embryos as determined by chi-square analysis (P < 0.05). This is the first study to recover in vivo derived human blastocysts following ovarian stimulation for embryo genetic characterization. Recovered blastocysts showed rates of chromosome euploidy similar to the rates found in the control IVF embryos. In 11 cycles (8.2%), detectable levels of hCG were present 13 days after IUI, which regressed spontaneously in two cases and declined after an endometrial curettage in two cases. Persistent hCG levels were resolved after methotrexate in three cases and four cases received both curettage and methotrexate.The first objective was to evaluate the feasibility of uterine lavage following ovarian stimulation to recover blastocysts for analysis, and that goal was achieved. However, the uterine lavage system was not completely optimized in our earlier experience to levels that were achieved late in the clinical study and will be expected in clinical service. The frequency of chromosome abnormalities of in vivo and IVF control embryos was similar, but this was a small-size study. However, compared to larger historical datasets of in vitro embryos, the in vivo genetic results are within the range of high-quality in vitro embryos.Uterine lavage offers a nonsurgical, minimally invasive strategy for recovery of embryos from fertile women who do not want or need IVF and who desire PGT, fertility preservation of embryos or reciprocal IVF for lesbian couples. From a research and potential clinical perspective, this technique provides a novel platform for the use of in vivo conceived human embryos as the ultimate benchmark standard for future and current ART methods.Previvo Genetics, Inc., is the sole sponsor for the Punta Mita, Mexico, clinical study. S.M. performs consulting for CooperGenomics. J.E.B. and S.A.C. are co-inventors on issued patents and patents owned by Previvo and ownshares of Previvo. S.N. is a co-author on a non-provisional patent application owned by Previvo and holds stock options in Previvo. S.T.N. and M.J.A. report consulting fees from Previvo. S.T.N., S.M., M.V.S., M.J.A., C.N. and J.E.B. are members of the Previvo Scientific Advisory Board (SAB) and hold stock options in Previvo. J.E.B and S. M are members of the Previvo Board of Directors. A.N. and K.C. are employees of Previvo Genetics. L.V.M, T.M.M, J.L.R and S. S have no conflicts to disclose.Protocol Registration and Results System (PRS) Trial Registration Number and Name: Punta Mita Study TD-2104: Clinical Trials NCT03426007.

  View details for DOI 10.1093/humrep/dez242

  View details for PubMedID 31886877

• Human Uterine Lavage: First Live Births from In Vivo Conceived Genetically Screened Blastocysts. Advances in therapy Najmabadi, S., Rivas, J. L., Angle, M. J., Nadal, A., Bastu, E., Munné, S., Carson, S. A., Buster, J. E., Nakajima, S. T. 2023

  Abstract

  We wish to report the first live births from genetically screened human euploid blastocysts obtained by uterine lavage. The embryos transferred to infertile women were previously obtained using a novel fully automated uterine lavage catheter and fluid recovery device developed for this indication. The objective of this portion of the research was to confirm embryo implantation and live births with these unique in vivo conceived blastocysts obtained by uterine lavage.In vivo conceived embryos recovered by uterine lavage 5 days after intrauterine insemination were available for embryo donation. In vivo embryos were the result of prior controlled ovarian stimulation cycles in oocyte donors and intrauterine insemination with donor sperm. An observational case series of nine embryo transfer procedures was performed at an outpatient fertility center. One to two embryos were transferred to eight infertile women since one woman had two separate embryo transfer procedures.Nine embryo transfer procedures were performed with 14 blastocysts in eight women resulting in a blastocyst implantation rate of 36% (5/14) and live birth rate of 44% (4/9). Five infants have been born from the four delivered pregnancies with one set of twins.This is the first report of live births from genetically screened human euploid blastocysts obtained by uterine lavage. The nonsurgical uterine lavage office procedure represents the only current approach to obtain in vivo conceived embryos and can provide a benchmark for comparison to standard in vitro cultured blastocysts. Live births of in vivo conceived blastocysts represent the validation that the nonsurgical uterine lavage procedure allows simplified access to naturally conceived embryos without performing the surgical procedure of an oocyte aspiration. Owing to its simplicity, uterine lavage may be useful in screening embryos for preimplantation genetic testing for aneuploidy in fertile and infertile couples.ClinicalTrials.gov (Identifier NCT03426007).

  View details for DOI 10.1007/s12325-023-02486-1

  View details for PubMedID 36988819

  View details for PubMedCentralID 8213447

• Relationship between paternal somatic health and assisted reproductive technology outcomes. Fertility and sterility Eisenberg, M. L., Li, S., Wise, L. A., Lynch, C. D., Nakajima, S., Meyers, S. A., Behr, B., Baker, V. L. 2016; 106 (3): 559-565

  Abstract

  To study the association between paternal medical comorbidities and the outcomes of assisted reproductive technology (ART).Retrospective cohort study.Academic reproductive medicine center.We analyzed fresh ART cycles uszing freshly ejaculated sperm from the male partner of couples undergoing ART cycles from 2004 until 2014. We recorded patient and partner demographic characteristics. The cohort was linked to hospital billing data to obtain information on selected male partners' comorbidities identified using ICD-9-CM codes.None.Fertilization, clinical pregnancy, miscarriage, implantation, and live-birth rates as well as birth weights and gestational ages.In all, we identified 2,690 men who underwent 5,037 fresh ART cycles. Twenty-seven percent of men had at least one medical diagnosis. Men with nervous system diseases had on average lower pregnancy rates (23% vs. 30%) and live-birth rates (15% vs. 23%) than men without nervous system diseases. Lower fertilization rates were also observed among men with respiratory diseases (61% vs. 64%) and musculoskeletal diseases (61% vs. 64%) relative to those without these diseases. In addition, men with diseases of the endocrine system had smaller children (2,970 vs. 3,210 g) than men without such diseases. Finally, men with mental disorders had children born at an earlier gestational age (36.5 vs. 38.0 weeks).The current report identified a possible relationship between a man's health history and IVF outcomes. As these are potentially modifiable factors, further research should determine whether treatment for men's health conditions may improve or impair IVF outcomes.

  View details for DOI 10.1016/j.fertnstert.2016.04.037

  View details for PubMedID 27179785

• Practice patterns, satisfaction, and demographics of reproductive endocrinologists: results of the 2014 Society for Reproductive Endocrinology and Infertility Workforce Survey FERTILITY AND STERILITY Barnhart, K. T., Nakajima, S. T., Puscheck, E., Price, T. M., Baker, V. L., Segars, J. 2016; 105 (5): 1281-1286

  Abstract

  To identify the current and future state of the practice of reproductive medicine.Cross-sectional survey.Not applicable.None.Not applicable.The survey included 57 questions designed to assess practice patterns/metrics and professional satisfaction and morale.A total of 336/1,100 (31%) responded, and they were 38% women, 61% men, and 76% Caucasian, with a mean age of 54. Respondents averaged 2.3 jobs and averaged 53 hours of work per week: 44% work in academia and 50% in private groups. Average practice size was 5.5, with an average of 470 fresh IVF cycles performed per year. Percent effort included 63% infertility, 10% endocrinology, 10% surgery, and 9% research. Respondents performed an average of 13 major surgeries, 69 minor surgeries, and 128 oocyte retrievals per year. A total of 60% were salaried, and 40% were equity partners. Compensation was highly skewed. Greater than 84% had a positive morale and had a positive view of the future, and 92% would again choose REI as a career. The most satisfying areas of employment were patient interactions, intellectual stimulation, interactions with colleagues, and work schedule. The least satisfying areas were work schedule and financial compensation. Training was felt to be too focused on female factor infertility and basic research with insufficient training on embryology, genetics, male factor infertility, and clinical research. In the next 5 years, 57% suggested that the need for specialists would stay the same, while 20% predicted a decrease. A total of 58% felt we are training the correct number of fellows (37% felt we are training a surplus). Compared with academia, those in private practice reported higher compensation, less major surgery, more IVF, less endocrinology, and less research. Men worked more hours, conducted more surgery and IVF cycles, and had higher compensation than women. Morale was similar across age, gender, practice type, and geography.Our subspecialty has an extremely high morale. We are a middle-aged subspecialty with disparate compensation and a focused practice. Some respondents sense a need for a change in our training, and most anticipate only mild growth in our field.

  View details for DOI 10.1016/j.fertnstert.2015.12.135

  View details for Web of Science ID 000375871200036

  View details for PubMedID 26774576

• Body mass index does not affect the efficacy or bleeding profile during use of an ultra-low-dose combined oral contraceptive. Contraception Nakajima, S. T., Pappadakis, J., Archer, D. F. 2016; 93 (1): 52-7

  Abstract

  Safe and effective contraceptive options for obese women are becoming more important due to the obesity epidemic within the United States. This study evaluated the impact of body mass index (BMI) on efficacy, safety and bleeding patterns during use of an ultra-low-dose combined oral contraceptive (COC).Data are from a Phase 3 clinical efficacy and safety study of an ultra-low-dose COC containing 1.0-mg norethindrone acetate and 10-mcg ethinyl estradiol. Pearl Indices, adverse events and bleeding profile were calculated for BMI ranges of <25, 25-30 and >30 kg/m(2).Of the 1581 participants included in the analysis, 28.3% were overweight, and 18.0% were obese. For women aged 18-45 years, the Pearl Indices were 2.49, 2.32 and 1.89 for women with a BMI <25, 25-30 and >30 kg/m(2), respectively. The ultra-low dose of ethinyl estradiol did not impact scheduled bleeding or intensity of bleeding, but we observed a slight decline in amenorrhea and slight increase in unscheduled bleeding in obese women compared with other BMI categories.Our analysis of an ultra-low-dose COC did not find clinically important differences in contraceptive failure rates, adverse events or bleeding profile with increasing BMI.Our analysis of an ultra-low ethinyl estradiol dose COC did not find clinically important differences in contraceptive failure rates, adverse events or bleeding profile with increasing BMI. An ultra-low-dose COC provides another safe and effective contraceptive option for obese women.

  View details for DOI 10.1016/j.contraception.2015.09.013

  View details for PubMedID 26410176

• Hormonal and Nonhormonal Treatment of Vasomotor Symptoms OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA Krause, M. S., Nakajima, S. T. 2015; 42 (1): 163-?

  Abstract

  This article focuses on the cause, pathophysiology, differential diagnosis of, and treatment options for vasomotor symptoms. In addition, it summarizes important points for health care providers caring for perimenopausal and postmenopausal women with regard to health maintenance, osteoporosis, cardiovascular disease, and vaginal atrophy. Treatment options for hot flashes with variable effectiveness include systemic hormone therapy (estrogen/progestogen), nonhormonal pharmacologic therapies (selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, clonidine, gabapentin), and nonpharmacologic therapy options (behavioral changes, acupuncture). Risks and benefits as well as contraindications for hormone therapy are further discussed.

  View details for DOI 10.1016/j.ogc.2014.09.008

  View details for Web of Science ID 000350936900014

  View details for PubMedID 25681847