Does timing matter when initiating elagolix in a natural menstrual cycle?

OBJECTIVE: To investigate the efficacy of elagolix when administered at different time points in a menstrual cycle. DESIGN: Clinical case series. SETTING: Academic reproductive endocrinology center. PATIENTS: Ovulatory women not desiring pregnancy. INTERVENTIONS: Six doses of elagolix 200 mg were administered over 4 days, starting at 3 different points in a menstrual cycle: early follicular; late follicular; and midluteal. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P) concentrations were measured at baseline, during elagolix administration, and 1 day after the last dose. Transvaginal ultrasounds were performed to monitor follicle sizes. MAIN OUTCOME MEASURES: Serum FSH, LH, E2, and P. RESULTS: Twelve women, four per group, completed the study. Subjects were 23-42 years of age. Demographics and ovarian reserve parameters were similar among participants. Elagolix suppressed FSH, LH, E2, and P when administered in the early follicular and midluteal phases but had mixed results when administered in the late follicular phase. Two participants demonstrated suppression of all four hormones. One participant ovulated, indicated by an increase in P concentration and development of a corpus luteum. A second participant did not ovulate yet demonstrated an increase in E2 concentration with growth of a dominant follicle. There were no significant differences in median percent change of hormone concentrations across study groups. CONCLUSIONS: The results of this study suggest that elagolix can suppress the hypothalamic-pituitary-ovarian axis when initiated at different points in a menstrual cycle. Optimal dosing and treatment window for consistent hormone suppression have yet to be determined. CLINICAL REGISTRATION NUMBER: NCT04060992.

Association of bioavailable inhibin B and oocyte yield in controlled ovarian stimulation.

OBJECTIVE: To determine if the biologically active or bioavailable inhibin B (bio-inhB) correlated with the oocyte yield in controlled ovarian stimulation (COS). DESIGN: Cross-sectional study. SETTING: Academic center. PATIENTS: Women undergoing oocyte cryopreservation. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum of women were sampled to measure bio-inhB at three points: baseline ("start"); middle ("mid"); and end of COS. A validated, highly specific enzyme-linked immunosorbent assay (Ansh Labs, Webster, TX) measured bio-inhB. The Spearman tests analyzed correlations between bio-inhB and other ovarian reserve markers, including age, follicle-stimulating hormone (FSH), antral follicle count (AFC), and antimüllerian hormone (AMH), and correlations between these markers and oocyte yield. RESULTS: A total of 144 women were included. Bioavailable inhibin B at the mid and end of COS, plus its delta, were strongly correlated with other ovarian reserve markers. As the bio-inhB concentration increased, the AFC and AMH levels also increased, whereas the FSH concentration and age decreased. Bioavailable inhibin B values, except at the start of COS, were more strongly correlated with oocyte yield than the FSH concentration (r = 0.72-0.82 vs. r = -0.44) and correlated similarly to the AFC and AMH concentration (r = 0.79 and 0.81, respectively). These correlations strengthened in those with diminished ovarian reserve, specifically age ≥35 years or AMH concentration <2 ng/mL (r = 0.71-0.86 vs. r = 0.49-0.67). CONCLUSIONS: Predicting COS outcome is imperfect. When using a highly specific enzyme-linked immunosorbent assay, bio-inhB correlated with the oocyte yield similar to or more strongly than traditionally used ovarian reserve markers. These correlations strengthened in cases of diminished ovarian reserve. Bioavailable inhibin B provides physicians with an additional clinical tool for estimating COS outcome.

Developmental potential of immature human oocytes aspirated after controlled ovarian stimulation.

PURPOSE: Intracytoplasmic sperm injection (ICSI) for initially immature oocytes that mature in vitro is controversial and practice varies widely. While it may increase the number of usable embryos, it may also be time-intensive and potentially low-yield. This study sought to elucidate which patients may benefit from ICSI of initially immature oocytes that matured in vitro. METHODS: A retrospective study comparing fertilization, cleavage, blastulation, and embryo usage rates between sibling initially immature and mature oocytes that underwent ICSI between 2015 and 2019 was performed. Outcomes of initially immature oocytes were stratified by initial maturation stage, timing of progression to metaphase II (MII) in vitro, percentage of mature oocytes in the cycle, and female age. RESULTS: Ten thousand eight hundred seventeen oocytes from 889 cycles were included. Of 3137 (29.0%) initially immature oocytes, 418 (13.3%) reached MII later on the day of retrieval (day 0) and 1493 (47.6%) on day 1. Overall, embryos originating from initially immature oocytes had lower cleavage and blastulation rates compared to those from initially mature oocytes (P<0.05, all groups). However, embryos from oocytes that matured later on day 0 comprised a unique subset that had clinically similar cleavage (75% vs 80%, RR 0.93, P=0.047) and blastulation rates (41% vs 50%, RR 0.81, P=0.024) compared to initially mature oocytes. Women with low percentages of mature oocytes in the cycle overall and women ≥40 in cleavage cycles derived the highest relative benefit from the use of immature oocytes. CONCLUSION: ICSI of immature oocytes, particularly those that mature later on the day of retrieval, may improve numbers of usable embryos. This study supports routine reassessment of immature oocytes for progression to MII and ICSI on day 0. An additional reassessment on day 1 may also be of use in older women or those with low percentage of mature oocytes.

Sperm Morphology: History, Challenges, and Impact on Natural and Assisted Fertility.

PURPOSE OF REVIEW: The classification of morphologically normal sperm has been progressively redefined. Concurrently, our understanding of the significance of sperm morphology in relation to male factor infertility has evolved. In this review, we will discuss the evolution of sperm morphology assessment and factors that contribute to its measurement variability. We will examine the impact of sperm morphology on natural pregnancy, IUI, IVF, and ICSI outcomes. RECENT FINDINGS: There is a lack of consensus on sperm morphology classification, technique, and inter-observer grading variability. Current evidence suggests sperm morphology has low predictive value for pregnancy success, for both natural and assisted reproduction. Additionally, the threshold for what is considered an adequate percentage of morphologically normal sperm has changed over time. These variables have called into question the relevance of this variable in predicting fertility outcomes. Our understanding of the impact of sperm morphology on reproductive outcomes continues to evolve and seems to play less of a role than initially thought.

Random Start Ovarian Stimulation for Oocyte or Embryo Cryopreservation in Women Desiring Fertility Preservation Prior to Gonadotoxic Cancer Therapy.

BACKGROUND: Women of reproductive age diagnosed with cancer are often interested in preserving gametes or reproductive tissue that would allow for future genetic parenthood. Preservation of fertility is often accomplished in young cancer patients via ovarian stimulation followed by oocyte or embryo cryopreservation. Conventional stimulation protocols, however, require 2-4 weeks to complete ovarian stimulation, oocyte retrieval and possible fertilization. Such a strategy may not be feasible in patients requiring urgent cancer treatment. Recent studies have highlighted that random start ovarian stimulation can be initiated irrespective of the phase of the menstrual cycle and is an attractive alternative to conventional ovarian stimulation. The primary aim of the current review is to discuss the feasibility and success of random start ovarian stimulation for oocyte or embryo cryopreservation in women desiring fertility preservation prior to gonadotoxic cancer therapy. METHOD: We performed a systematic review of medical literature published between January 2000 to June 2017 reporting the utility of random start ovarian stimulation for fertility preservation. Search terms included "fertility preservation," "cancer," "ovarian stimulation," "random-start ovarian stimulation," "embryo cryopreservation, and" "oocyte cryopreservation." Publications were included in this review only if patients underwent random start ovarian stimulation prior to cancer therapy. RESULTS: Nineteen publications were identified and perused by the authors. Most publications described the utility of random start ovarian stimulation in the setting of breast cancer. Radom-start stimulation was associated with a reduced time interval between ovarian stimulation initiation and oocyte or embryo cryopreservation. The yield of mature oocytes and their developmental potential into embryos was comparable between conventional and random-start protocols, albeit with higher gonadotropin doses in the latter. CONCLUSION: The current review suggests that random start ovarian stimulation can shorten the interval between ovarian stimulation and oocyte retrieval, with the yield of oocytes and embryos being comparable to conventional stimulation protocols. Thus, random start ovarian stimulation may serve as a better option for fertility preservation in patients requiring urgent cancer treatment.

Postpartum Permanent Sterilization: Could Bilateral Salpingectomy Replace Bilateral Tubal Ligation?

STUDY OBJECTIVE: There has recently been an expansion in the use of bilateral salpingectomy at the time of sterilization to theoretically decrease ovarian cancer risk. We sought to determine if postpartum salpingectomy is equivalent to postpartum bilateral tubal ligation (BTL) in terms of duration, estimated blood loss (EBL), and complication rate. DESIGN: A retrospective case series (Canadian Task Force Classification II-2). SETTING: An academic inner-city hospital. PATIENTS: All patients admitted for delivery of full-term intrauterine pregnancy desiring permanent sterilization between March 2014 and March 2015 were included. Excluded patients included those who had sterilization at the time of the cesarean section or other surgical procedure. Two cohorts were identified, those who had a planned postpartum tubal ligation and those having a postpartum salpingectomy. INTERVENTIONS: Postpartum sterilization. MEASUREMENTS AND MAIN RESULTS: Researchers of this study recorded demographics, medical histories, and abdominal surgical histories for all patients who met the inclusion criteria. Surgical times, EBL, and complication rates were reviewed. Unpaired t test calculations were used to identify differences between age, body mass index, parity, and surgical time between the 2 cohorts. Chi-square tests were used to determine the statistical significance between complication rates, history of abdominal surgery, and past medical history of tubal disease between the 2 cohorts. Eighty women were identified, 64 in the BTL group and 16 in the salpingectomy cohort. The demographics of each cohort were equivocal. The average surgical time was 59.13 and 71.44 minutes in the BTL and salpingectomy cohorts, respectively. Of the 80 patients, only 1 had an EBL greater than 50 mL; this patient was in the BTL group. Four complications were noted in the BTL cohort, but none were evident in the salpingectomy group. There were no documented sterilization failures in the follow-up period (median = 9 months). CONCLUSION: Postpartum salpingectomy is slightly longer in duration but with similar blood loss and complication rates. Salpingectomy could be considered in particularly high-risk patients at risk for ovarian cancer when consenting for a postpartum sterilization procedure.

Should all oocyte donors receive prophylactic antibiotics for retrieval?

In a retrospective study comparing 526 oocyte donors who received prophylactic antibiotics for oocyte retrieval with a comparable group of 625 who did not, the incidence of infection after retrieval was reduced from 0.4% to 0 in the group receiving antibiotics. Donors take risks but have no medical indication for the procedures that they undergo; our data suggest that prophylactic antibiotics at retrieval should be considered to minimize the risk of infection.