GnRH agonist early follicular challenge test as a predictor of ovarian response in antagonist cycles for fertility preservation.

The aim of our study was to evaluate if the response to follicular GnRH agonist (GnRHa) trigger be used to predict intracycle ovarian response in GnRH antagonist cycles among women undergoing fertility preservation IVF. We conducted a prospective study of 146 GnRH antagonist oocyte pickup (OPU) cycles to evaluate GnRHa stimulation test (GAST). On day 2 of the cycle, basal E2 were measured, followed by injection of 0.2 mg GnRHa as part of the initial ovarian stimulation. 12 h later blood sampling was repeated (GAST E3). E2 response was used as test parameter. The major outcome was the number of mature cryopreserved oocytes. We found a linear correlation between both GAST E3 level and GAST E3/E2 ratio and number of M2 oocytes. ROC curve analysis of GAST E3, GAST E3/E2 ratio, AFC and day 3 FSH for > 15 M2 and < 5 M2 oocytes was calculated. For GAST E3 levels obtaining < 5 M2 oocytes, an AUC value of 0.79 was found. For GAST E3 levels obtaining > 15 M2 oocytes, AUC value of 0.8. Patients with GAST E3 ≤ 384 pmol/l has 58.6% risk to obtain < 5 oocytes. Patients younger than 35 with GAST E3 > 708 pmol/l have 66% chance for freezing > 15 oocytes. The response to single GnRHa administration during GnRH antagonist cycle can be used as biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict the response of the specific cycle, and can potentially be used to adjust the treatment dose.Trial registration number: 0304-20-ASF.

Follicular challenge test to predict suboptimal response to gonadotropin releasing hormone agonist trigger in elective oocyte cryopreservation cycles.

This prospective study aimed to test the ability of follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger, assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program. The study included 91 women that underwent non-medical fertility preservation. On day two to menstrual cycle, blood tests were drawn (basal Estradiol, basal FSH, basal LH, Progesterone) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist (FACT) and arrive for repeated blood workup 10-12 h later in the next morning, followed by a flexible antagonist protocol. LH levels on the morning after ovulation trigger were compared to FACT LH levels. The results demonstrated that LH levels following agonist ovulation trigger below 15IU/L occurred in 1.09% of cycles and were predicted by FACT, r = 0.57, p < 0.001. ROC analysis demonstrated that FACT LH > 42.70 IU/L would predict LH post trigger of more than 30 IU/L with 75% sensitivity and 70% specificity, AUC = 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p < 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the number of frozen oocytes was progesterone levels post agonist trigger (r = 0.746, p < 0.001). We concluded that suboptimal response to agonist trigger, as assessed by post trigger LH levels was a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate LH levels elevation after agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders.

The impact of past COVID-19 infection on pregnancy rates in frozen embryo transfer cycles.

PURPOSE: To study the effect of SARS-CoV-2 infection on pregnancy rates in frozen embryo transfer (FET) cycles. METHODS: A retrospective cohort study including women under the age of 42 with documented SARS-CoV-2 infection up to 1 year prior to treatment, undergoing FET cycles in the first half of 2021, with transfer of embryos generated prior to the infection. Controls were SARS-CoV-2 non-diagnosed, non-vaccinated women matched by age, number, and day of embryo transfer. Demographic and cycle characteristics and outcomes were compared. RESULTS: Forty-one recovered women and 41 controls were included. Pregnancy rates were 29% and 49% respectively (p = 0.070). Stratification by time from SARS-CoV-2 infection to transfer into ≤ 60 and > 60 days revealed a difference in pregnancy rates, with women in the COVID group having lower pregnancy rates if infected in proximity to the transfer (21% vs. 55%; p = 0.006). In a logistic regression model, infection was a significant variable (p = 0.05, OR 0.325, 95% CI 0.106-0.998). Logistic regression applied on the subgroup of women infected in proximity to the transfer further strengthened the univariate results, with COVID-19 remaining a significant parameter (p = 0.005, OR 0.072, 95% CI 0.012-0.450). CONCLUSIONS: In FET cycles of patients with past SARS-CoV-2 infection, in which oocytes were retrieved prior to infection, decreased pregnancy rates were observed, specifically in patients who recovered less than 60 days prior to embryo transfer. Pending further studies, in cases of FET cycles with limited number of embryos, postponing embryo transfer for at least 60 days following recovery from COVID-19 might be considered when feasible.

Coronavirus disease 2019 vaccination and infertility treatment outcomes.

OBJECTIVE: To assess the influence of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid vaccine on ovarian response and in vitro fertilization (IVF) treatment outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary university-affiliated medical center and a private medical center. PATIENT(S): The study included a total of 400 patients, 200 vaccinated women and 200 age-matched unvaccinated women, who underwent IVF in January-April 2021. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The mean number of oocytes retrieved and clinical pregnancy rates in vaccinated vs. unvaccinated patients. RESULT(S): A total of 200 patients underwent oocyte retrieval 14-68 days after receiving COVID-19 vaccination. No difference was found in the mean number of oocytes retrieved per cycle (10.63 vs. 10.72) between vaccinated and unvaccinated patients. Among 128 vaccinated and 133 unvaccinated patients who underwent fresh embryos transfers, no difference was demonstrated in the clinical pregnancy rates (32.8% vs. 33.1%), with 42 and 44 clinical pregnancies, respectively. The fertilization rates and mean number of cryopreserved embryos were similar between the 2 groups in freeze-all cycles (55.43% vs. 54.29% and 3.59 vs. 3.28, respectively). Among vaccinated and unvaccinated patients who underwent fresh embryo transfers, no difference was noted in the fertilization rate (64.81% vs. 61.98%) and transferred embryos' quality. Regression models applied demonstrated no effect of the vaccine on oocyte yields and pregnancy rates. CONCLUSION(S): The COVID-19 messenger ribonucleic acid vaccine did not affect the ovarian response or pregnancy rates in IVF treatment. Women should be vaccinated for COVID-19 before attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women.

IVF under COVID-19: treatment outcomes of fresh ART cycles.

STUDY QUESTION: Does prior severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women undergoing fertility treatments affect the outcomes of fresh ART cycles? SUMMARY ANSWER: SARS-CoV-2 infection does not affect fresh ART treatment outcomes, except for a possible long-term negative effect on oocyte yield (>180 days postinfection). WHAT IS KNOWN ALREADY: A single previous study suggested no evidence that a history of asymptomatic or mild SARS-CoV-2 infection in females caused impairment of fresh ART treatment outcomes. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study, including all SARS-CoV-2 infected women who underwent fresh ART cycles within a year from infection (the first cycle postinfection), between October 2020 and June 2021, matched to non-diagnosed controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients from two large IVF units in Israel who were infected with SARS-CoV-2 and later underwent fresh ART cycles were matched by age to non-diagnosed, non-vaccinated controls. Demographics, cycle characteristics and cycle outcomes, including oocyte yield, maturation rate, fertilization rate, number of frozen embryos per cycle and clinical pregnancy rates, were compared between groups. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred and twenty-one infected patients and 121 controls who underwent fresh ART cycles were included. Oocyte yield (12.50 versus 11.29; P = 0.169) and mature oocyte rate (78% versus 82%; P = 0.144) in all fresh cycles were similar between groups, as were fertilization rates, number of frozen embryos per cycle and clinical pregnancy rates (43% versus 40%; P = 0.737) in fresh cycles with an embryo transfer. In a logistic regression model, SARS-CoV-2 infection more than 180 days prior to retrieval had a negative effect on oocyte yield (P = 0.018, Slope = -4.08, 95% CI -7.41 to -0.75), although the sample size was small. LIMITATIONS, REASONS FOR CAUTION: A retrospective study with data that was not uniformly generated under a study protocol, no antibody testing for the control group. WIDER IMPLICATIONS OF THE FINDINGS: The study findings suggest that SARS-CoV-2 infection does not affect treatment outcomes, including oocyte yield, fertilization and maturation rate, number of good quality embryos and clinical pregnancy rates, in fresh ART cycles, except for a possible long-term negative effect on oocyte yield when retrieval occurs >180 days post-SARS-CoV-2 infection. Further studies are warranted to support these findings. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: 0010-21-HMC, 0094-21-ASF.

Acute Adnexal Torsion: Is Immediate Surgical Intervention Associated with a Better Outcome?

OBJECTIVES: We aimed to investigate whether surgery for adnexal detorsion within 6 h from admission to the hospital was associated with less adnexal ischemia. DESIGN: This is a retrospective cohort study. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: This retrospective study was conducted at two university-affiliated medical centers and assessed women aged 18-45 years with adnexal torsion who were hospitalized within 12 h from the pain onset and underwent surgery for detorsion within 24 h. The study group was divided into 2 groups: early, surgical intervention within less than 6 h and late, surgical intervention between 6 and 24 h. The primary outcome was the rate of macroscopic appearance of ischemic adnexa. RESULTS: Two hundred and twenty women fulfilled the inclusion criteria. In 101 women, the adnexa with the torsion appeared macroscopically ischemic. There was no difference in ischemic adnexa between the early and late intervention groups (48% vs. 40%; p = 0.269). No significant association was found between the physical examination or ultrasonographic findings and the rate of ischemic adnexa within each group. LIMITATIONS: The main limitations of our study are its retrospective nature. Much of the clinical and ultrasonographic data are subjective and operator-dependent. The decision to operate may vary from one surgeon to another. CONCLUSION: Immediate surgical intervention in patients with adnexal torsion is not associated with a lower rate of adnexal ischemia. These findings suggest that in acute adnexal torsion, there is a wider time window for a thorough evaluation before surgery.

Are Ultrasonographic Findings Suggestive of Ovarian Stromal Edema Associated with Ischemic Adnexal Torsion?

OBJECTIVE: To study whether sonographic findings suggestive of ovarian stromal edema are associated with tissue ischemia in patients with adnexal torsion. METHODS: A study of 79 patients with adnexal torsion was performed. Patients were divided into an ischemic group, in which the twisted adnexa were seen as blue or black, and a non-ischemic group, in which the adnexa retained normal color and appeared viable. Clinical and ultrasonographic findings, specifically the presence of ultrasonographic signs suggestive of ovarian stromal edema, were compared between the two groups. RESULTS: Of the 79 patients with torsion, in 44 (55.7%) the adnexa appeared ischemic at surgery. The presence of ischemia was not associated with age, pregnancy, duration of pain, vomiting or findings at physical examination. There was no significant difference between the ischemic and the non-ischemic group in the proportion of patients with signs of ovarian stromal edema (59 vs. 40%, p = 0.11), in the proportion of patients with absent/diminished stromal Doppler flow (36 vs. 28%, p = 0.12%) or in the proportion of patients with both signs of stroma edema and absent/diminished stromal Doppler flow (20 vs. 12%, p = 0.36). CONCLUSION: Ultrasonographic signs of ovarian stromal edema do not assist in differentiating between ischemic and non-ischemic adnexal torsion.