Use of fertility preservation services in female reproductive-aged cancer patients.

OBJECTIVE: The objective of the study was to determine the rates and predictors of fertility preservation services among reproductive-aged women with common cancers in the United States. STUDY DESIGN: We used the MarketScan database to identify women 18-45 years of age with lung, breast, colorectal, or cervical cancer who underwent surgery and chemotherapy from 2009 through 2016. Services from 3 months before to 3 months after chemotherapy for evaluation for fertility preservation, laboratory testing for fertility evaluation, and fertility-preserving procedures were captured. Multivariable models were used to assess the factors associated with the use of fertility-preservation services. RESULTS: A total of 18,781 women, including 386 cervical, 1372 colorectal, 246 lung, and 16,777 with breast cancer, were identified. In women 18-35 years old, 11.7% underwent evaluation for fertility preservation, 13.7% underwent laboratory testing, and 6.3% pursued fertility-preserving procedures. The rates of office evaluation, laboratory testing, and performance of procedure were 3.3%, 7.5%, and 1.9 % in women aged 36-40 years and 0.5%, 7.2%, and 0.3% in those aged 41-45 years, respectively. The rate of fertility preservation evaluation rose from 1.0% in 2009 to 5.5% in 2016 (risk ratio, 4.66, 95% confidence interval, 2.38-9.11) while use of fertility-preserving procedures increased from 1.0% to 4.6% (risk ratio, 3.84, 95% confidence interval, 1.94-7.59) during the same time period. In a multivariable model, use of any fertility-preserving interventions were more common in patients with breast cancer (adjusted risk ratio, 2.30, 95% confidence interval, 1.30-4.06), those in the Northeast (adjusted risk ratio, 1.24, 95% confidence interval, 1.10-1.40), and in younger women (18-35 years) (adjusted risk ratio, 2.59, 95% confidence interval, 2.32-2.89). CONCLUSION: Although limited by lack of information regarding cancer stage and desire for future fertility, only a small fraction of reproductive-aged female cancer patients receiving chemotherapy are evaluated in a nationwide sample for fertility preservation or undergo fertility-preserving procedures.

Minimizing mosaicism: assessing the impact of fertilization method on rate of mosaicism after next-generation sequencing (NGS) preimplantation genetic testing for aneuploidy (PGT-A).

PURPOSE: Advances in preimplantation genetic testing (PGT) have led to practice changes in assisted reproductive technologies (ART), enabling fertility centers to transfer single embryos while maintaining excellent ongoing pregnancy rates, reducing miscarriage rates, and dramatically reducing ART-associated multiple pregnancies. The introduction of next-generation sequencing (NGS) allows PGT laboratories to assess for embryo mosaicism-although the true incidence and reproductive potential of predicted mosaic embryos are controversial. Due to concern for genetic contamination from other spermatozoa, most reference laboratories require use of intracytoplasmic sperm injection (ICSI) for single gene preimplantation genetic diagnosis (PGT-M). However, in PGT for aneuploidy (PGT-A), conventional insemination (IVF) is typically permissible. The purpose of this study was to evaluate rates of euploid, aneuploid, and mosaic in trophectoderm biopsy samples from embryos in IVF versus ICSI PGT-A cycles. Secondary aims were to assess sex ratio, and subtypes of aneuploidy and mosaicism in IVF versus ICSI PGT-A cycles. METHODS: We performed a retrospective review of women undergoing PGT-A at a single academic fertility center from July 1, 2015, to September 1, 2017. In all cycles, PGT-A was performed via trophectoderm biopsy on day 5 or 6 and analyzed using NGS at a single reference lab. We collected and compared patient demographics, fertility testing, cycle characteristics, and PGT-A outcomes between IVF and ICSI cycles. RESULTS: Three hundred two PGT-A cycles were included for analysis: 75 IVF and 227 ICSI cycles, resulting in 251 IVF and 724 ICSI biopsied blastocysts. Mean oocyte age of included cycles was 38.6 years (IVF) and 38.5 years (ICSI), p = 0.85. Baseline characteristics of IVF and ICSI PGT-A cycles were similar with the exception of semen parameters: IVF cycles had higher sperm concentration and total motility compared to ICSI cycles. PGT-A outcomes did not differ between IVF and ICSI cycles: euploid 27.9% (IVF) versus 30% (ICSI); aneuploid 45.4% (IVF) versus 43.1% (ICSI); no result 4.4% (IVF) versus 6.2% (ICSI). Though not significant, we identified a trend toward higher rate of mosaicism in IVF (25.9%) versus ICSI (20.9%). Among mosaic embryos, a lower percentage of simple mosaic embryos resulted from IVF (53.8%) versus ICSI (70.2%). Among aneuploid embryos, a non-significant higher percentage of complex aneuploidy resulted from IVF (16.3%) versus ICSI (9%). IVF resulted in a non-significant higher proportion of cycles with no transferrable embryos (42.7%) versus ICSI (36.6%). Numerical and sex chromosome involvement in mosaicism and aneuploidy were similar between IVF and ICSI cycles. CONCLUSION: IVF and ICSI NGS PGT-A have similar rates of euploid, aneuploid, and no result embryos, though IVF may result in higher rates of mosaicism and demonstrates differences in proportions of mosaic and aneuploid subtypes compared to ICSI. ICSI may be preferable to conventional insemination to minimize the rate of mosaic results in NGS PGT-A cycles.

Low estradiol responses in oocyte donors undergoing gonadotropin stimulation do not influence clinical outcomes.

PURPOSE: To examine the effect of low and very low estradiol responses in oocyte donors receiving gonadotropins on clinical outcomes of donor in vitro fertilization (IVF) cycles and to identify possible mechanisms responsible for low estradiol response. METHODS: This is a retrospective cohort study of oocyte donors undergoing antagonist IVF cycles with progression to oocyte retrieval between January 2010 and December 2016 at a single urban academic fertility center. Oocyte yield, fertilization rate, blastocyst rate, percentage of normal embryos on preimplantation genetic screening (PGS), pregnancy outcomes, and follicular fluid steroid profiles were compared between donors with normal estradiol response and those with low estradiol response. RESULTS: Three hundred sixty-six antagonist oocyte donor IVF cycles were identified: 42 cycles had a normal estradiol response (NE2), defined as peak serum estradiol (E2) of over 200 pg/mL per retrieved oocyte; 140 cycles had an intermediate estradiol response (iE2), defined as peak serum E2 between 100 and 200 pg/mL per retrieved oocyte; 110 cycles had a low estradiol response (LE2), defined as peak serum E2 between 50 and 100 pg/mL per retrieved oocyte; and 74 cycles had a very low estradiol response (vLE2), defined as peak serum E2 less than 50 pg/mL per retrieved oocyte. LE2 cycles resulted in a greater number of mature oocytes (22.4 vs. 13.6, p < 0.017), and fertilizations versus NE2 donors (18.5 vs. 10.7, p < 0.017), although the number of transferred or cryopreserved blastocysts were similar between groups (8.6, 6.9 vs. 4.8, p = 0.095, p = 1). The percentage of chromosomally normal embryos after PGS was similar between LE2, vLE2, and NE2 cycles (66.4, 71.8 vs. 63.1%, p = 0.99, p = 1). Pregnancy outcomes were similar between LE2, vLE2, and NE2 cycles. Serum AMH obtained on the day of peak E2 was similar to baseline serum AMH and did not differ between LE2 versus NE2 cycles. Follicular fluid E2 levels paralleled serum E2 levels and were lower in LE2 cycles versus NE2 cycles. CONCLUSION: The prevalence of very low E2 responses in donors appears to be high (20.2%). In contrast to autologous IVF cycles, LE2 does not portend poor outcomes in oocyte donors.

Repeated doses of GnRH antagonist at midcycle in artificial frozen embryo transfer cycles may not affect pregnancy outcomes.

No significant differences in outcomes have been found between protocols of endometrial preparation for frozen embryo transfer (FET), though gonadotropin releasing hormone (GnRH) antagonists may have detrimental effects on the endometrium. We conducted a retrospective cohort noninferiority study at a single academic center of women receiving multiple doses of mid-cycle GnRH antagonist (GAnt) to those receiving GnRH agonist (GAg) to determine if there are detrimental effects of GnRH antagonists. 1047 FET cycles were identified, detailed data was available in 840 cycles: 610 GAg and 230 GAnt cycles. Patients undergoing GAnt cycles were older (40 ± 6.6 versus 37 ± 5.1 years, p < 0.0001), more often used donor oocyte (36% versus 18.6%, p < 0.0001), and more often exhibited diminished ovarian reserve (49.1% versus 36.2%, p = 0.0009). Clinical pregnancy rates (CPRs) per transfer and implantation rates (IRs) were similar for GAnt and GAg cycles. There was a trend for higher pregnancy and IRs with GAg cycles in younger women (CPR 38.8% versus 26.7%, p = 0.16; IR 36% versus 23.3%, p = 0.07). Stratifying by diagnosis, CPR and IR were similar in GAnt and GAg cycles. A GAnt protocol of endometrial preparation for FET is not inferior to a GAg protocol regardless of patient age, use of donor oocyte, or infertility diagnosis.

Robotically assisted delayed total laparoscopic hysterectomy for placenta percreta.

BACKGROUND: The prevalence of morbidly adherent placenta has dramatically increased in the setting of the rising cesarean rate in the United States. Delayed surgical management of placenta accreta and its variants is emerging as methods that may significantly decrease bleeding and perioperative complications; however, optimal surgical approaches have not yet been determined. In this report, we present a case of robotic-assisted delayed interval hysterectomy in a patient with placenta percreta. METHOD: A minimally invasive approach, via a robotic-assisted total laparoscopic hysterectomy, was utilized for a 39-year-old gravida 9 para 3 with placenta percreta with placenta left in situ ten weeks after a tertiary cesarean section. EXPERIENCE: The robotic approach provided excellent visualization to facilitate fine planes of dissection, lower than expected estimated blood loss, and faster recover times when compared with conventional surgical approaches traditionally utilized for interval hysterectomies for placenta percreta. CONCLUSION: Robotic-assisted hysterectomy may be considered as an alternative to laparotomy for the delayed interval surgical management of morbidly adherent placenta percreta.