High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

PURPOSE: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). METHODS: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. RESULTS: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000-1999 pg/mL and 1000-1999 pg/mL versus 2000-2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999 pg/mL versus 3000-3999 pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9-1.04). CONCLUSION: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

Live birth associated with peak serum estradiol levels in letrozole intrauterine insemination cycles.

OBJECTIVE: To identify whether the serum estradiol (E2) level on the day of human chorionic gonadotropin (hCG) trigger or luteinizing hormone (LH) surge (hCG-LH) was associated with the live birth rate (LBR) during ovulation induction (OI) or controlled ovarian hyperstimulation with letrozole followed by intrauterine insemination (IUI). DESIGN: Retrospective cohort study. SETTING: Large, multicenter private practice. PATIENT(S): A total of 2,368 OI-IUI cycles in patients treated with letrozole followed by IUI were evaluated from January 1, 2014, to July 31, 2019. INTERVENTION(S): Ovulation induction with letrozole, followed by autologous IUI. MAIN OUTCOME MEASURE(S): The primary outcome measure was the LBR as a function of the serum E2 level at the time of hCG administration or LH surge, adjusting for age, body mass index, the largest follicle diameter, and the number of follicles ≥14 mm in diameter. The clinical pregnancy rate as a function of the E2 level, pregnancy rate as a function of the lead follicle diameter, and pregnancy loss rates were the secondary outcome variables. RESULT(S): A total of 2,368 cycles met the inclusion criteria. Outcomes were evaluated at the 25th (E2 level, 110 pg/mL), 50th (157 pg/mL), 75th (225 pg/mL), and 90th (319 pg/mL) percentiles. The LBRs ranged from 9.4% to 11.1% in the lower E2 cohorts and from 12.5% to 13.5% in the higher E2 cohorts. The LBR was significantly greater in the cohort of women with higher E2 levels in all percentile comparisons except for the 90th percentile. The mean periovulatory follicle diameter of ≥20 or <20 mm was not independently associated with the LBR or clinical pregnancy rate, despite a significantly higher mean E2 level in the larger follicle group. CONCLUSION(S): In letrozole OI cycles followed by IUI, lower LBRs and clinical pregnancy rates were found in women with lower E2 levels than in those with higher E2 levels at the 25th, 50th, and 75th percentile E2 level quartiles. Where possible, delaying hCG trigger until the E2 level increases after aromatase inhibition and approaches the physiologic periovulatory level may improve the pregnancy rates with letrozole followed by IUI.

Laparoscopic Hemi-hysterectomy and Trachelectomy in a Case of Herlyn-Werner-Wunderlich Syndrome.

BACKGROUND: Herlyn-Werner-Wunderlich Syndrome (HWWS) is a rare Müllerian anomaly characterized by uterus didelphys coexisting with an obstructed hemivagina and ipsilateral renal agenesis. CASE: A 13-year-old female presented one-year after menarche with severe dysmenorrhea and a right-sided pelvic mass. Imaging identified a right uterus with hematometra, hematocolpos, absent right kidney, normal left kidney, ureter, left uterus, and vagina compressed to the left by right hematocolpos. We performed laparoscopic hemi-hysterectomy of the non-communicating hemi-uterus, and laparoscopic trachelectomy. CONCLUSION: Laparoscopic hemi-hysterectomy and trachelecotmy is a minimally invasive surgical option for patients with Herlyn-Werner-Wunderlich Syndrome.

Embryo Transfer Catheter Contamination With Intravaginal Progesterone Preparations in a Simulated Embryo Transfer Model Impairs Mouse Embryo Development: Are There Implications for Human Embryo Transfer Technique?

OBJECTIVES: To study the effect of embryo transfer (ET) catheter contact with intravaginal progesterone preparations on mouse embryo development. STUDY DESIGN: In a simulated ET model, ET catheters were loaded with culture medium, placed in contact with intravaginal progesterone gel (Crinone 8%) or micronized progesterone intravaginal inserts (Endometrin 100 mg), and the intracatheter culture medium flushed. Embryos were cultured in the flushed culture medium at variable dilutions for variable lengths of time. Proportion of embryos progressing to blastocyst, embryo cell number, and apoptotic index was analyzed. RESULTS: None of the embryos cultured in undiluted progesterone-exposed medium progressed to blastocyst. The likelihood of achieving blastocyst status and the average embryo cell number increased significantly as culture media exposed to intravaginal progesterone was diluted. A significant decrease in cell number became apparent between 1 and 2 hours of exposure. Interestingly, the apoptotic index was significantly higher in progesterone-exposed embryos as compared to unexposed embryos. CONCLUSION: The contamination of ET catheter with intravaginal progesterone significantly impairs mouse embryo development, likely due in part to increased programmed cell death.

Elevated human chorionic gonadotropin and hyperandrogenemia in a woman with Müllerian agenesis.

BACKGROUND: Müllerian agenesis is a congenital malformation characterized by absence of the uterus, cervix, and upper vagina. A positive home pregnancy test in a woman with Müllerian agenesis mandated evaluation for malignancy. CASE: A woman with Müllerian agenesis presented with elevated levels of human chorionic gonadotropin (hCG), testosterone, and dehydroepiandrosterone sulfate. Pelvic magnetic resonance imaging (MRI), abdominal and pelvic computed tomography scan, chest computed tomography scan, brain MRI, and body positron emission tomography scan did not identify a malignancy. Human chorionic gonadotropin characterization revealed 74% hyperglycosylated and 1.6% free ß-hCG, suggesting a trophoblast-containing tumor. Interventional ovarian venous sampling and repeat pelvic MRI suggested a right adnexal source. After laparoscopic removal of a stage 1C right ovarian dysgerminoma, hCG and testosterone returned to normal. CONCLUSION: A dysgerminoma coincident with Müllerian agenesis expressed hCG before detection by MRI. Human chorionic gonadotropin molecular characterization, ovarian vein sampling, and repeat pelvic MRI led to successful treatment.

Infertility evaluation and treatment among women in the United States.

OBJECTIVE: To examine the characteristics of women seeking infertility evaluation and treatment. DESIGN: Cross-sectional survey based on in-person interviews, followed by two-step hurdle analysis. SETTING: Not applicable. PATIENT(S): 4,558 married or cohabitating women ages 25 to 44 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Likelihood of seeking a preliminary infertility evaluation and of seeking infertility treatment once evaluated, and the treatment type provided. RESULT(S): Of 623 women (13.7%) who reported seeking an infertility evaluation, 328 reported undergoing subsequent infertility treatment. Age at marriage, marital status, education, health insurance status, race/ethnicity, and religion were associated with the likelihood of seeking infertility evaluation. For example, the predicted probability that a non-white woman who married at age 25 will seek evaluation was 12%. This probability increased to 34% for white women with a graduate degree who had married at age 30. Among women who were evaluated, income, employment status, and ethnicity correlated strongly with the likelihood of seeking infertility treatment. Infertility drug therapy was the most frequent treatment used, and reproductive surgery and in vitro fertilization (IVF) were used the least often. CONCLUSION(S): The use of infertility services is not random. Understanding the sociodemographic factors correlated with use may assist new couples with family planning. Roughly 50% of the women evaluated for infertility progressed to treatment, and only a small proportion were treated with more advanced assisted reproductive technologies such as in vitro fertilization. Future research aimed at improving access to effective health-care treatments within the boundaries of affordability is warranted.

Endometrial polyps in reproductive-age fertile and infertile women.

Endometrial polyps are a frequent finding in infertile patients. Little is known about the true prevalence of polyps in infertile patients. It is unproved whether polyps are causative of infertility, or whether surgical polypectomy by hysteroscopy improves the likelihood of successful conception. This article reviews endometrial polyps in reproductive-age fertile and infertile women.

Cannulation of a resistant internal os with the malleable outer sheath of a coaxial soft embryo transfer catheter does not affect in vitro fertilization-embryo transfer outcome.

OBJECTIVE: To assess the impact of cannulation of a resistant cervical os with the outer malleable sheath of a double-lumen, soft ET catheter on IVF-ET outcomes. DESIGN: Retrospective cohort study. SETTING: University-based IVF center. PATIENT(S): One hundred forty-two patients undergoing 142 ETs. INTERVENTION(S): Trial ultrasound-guided ET at all transfers, leaving the malleable outer sheath in situ when the soft inner catheter could not negotiate the internal os. MAIN OUTCOME MEASURE(S): Implantation rate and clinical pregnancy rate. RESULT(S): In 102 ETs (71.8%), the soft inner sheath easily negotiated the internal os (group 1). Forty ETs (28.2%) required cannulation of resistant internal ora with the outer sheath of the trial catheter (group 2). Implantation rates (35% vs. 32% in groups 1 and 2, respectively) and clinical pregnancy rates (50% vs. 45%) were not significantly different between groups. Blood was present on the transfer catheter after ET more frequently in group 2 than in group 1 (55% vs. 15%); however, neither the implantation rate nor the clinical pregnancy rate were affected by the presence of blood. CONCLUSION(S): Cannulation of a resistant internal os by the malleable outer sheath and blood on the transfer catheter after ET do not have an adverse effect on implantation rate or clinical pregnancy rate.