Fertility outcomes in women undergoing Assisted Reproductive Treatments after COVID-19 vaccination: A prospective cohort study.

BACKGROUND: Vaccination against Coronavirus-19 disease (COVID-19) was widely administered from 2021 onwards. There is little information on how this vaccine affected fertility after assisted-reproductive-technology (ART). The aim of this study therefore was to determine if COVID-19 vaccination or time-since-vaccination influenced ART outcomes. MATERIALS AND METHODS: In this prospective cohort study, 502 oocyte-retrieval-cycles and 582 subsequent embryo- transfer-cycles were grouped based on COVID-19 vaccine status of the female partner into those with no-exposure, 1-dose and ≥2-dose exposure. Within the exposed cohort, time-since-last-vaccination to embryotransfer- cycle (Ttr) was calculated in days. Main outcomes were mean-total-utilizable-embryos, mean-oocyteutilization- rates and cumulative-ongoing-pregnancy-rates per oocyte-retrieval-cycle, and ongoing-pregnancy and pregnancy-loss-rates per embryo-transfer cycle. The Beta-coefficient (ß) was calculated using linear regression for mean-total-utilizable-embryos and mean-oocyte-utilization-rates and adjusted-odds-ratio (OR) was calculated for cumulative-ongoing-pregnancy-rates, ongoing-pregnancy and pregnancy-loss-rates using binomial logistic regression. Influence of T(tr) on embryo-transfer outcomes was estimated using receiver-operator-curve (ROC) analysis and cut-offs determined that influenced embryo-transfer outcomes. RESULTS: Mean-total-utilizable-embryos and mean-oocyte-utilization-rate per oocyte-retrieval-cycle in no-exposure, 1-dose and ≥2 dose were 2.7 ± 1.8 vs. 2.5 ± 1.9 vs. 2.7 ± 2.0, P=0.78, (ß=0.42, 95% confidence-interval (CI)=0.15 to 0.69) and 21.2 ± 13.2 vs. 25.1 ± 19.0 vs. 26.7 ± 18.8, P=0.08, (ß=3.94, 95% CI=1.26 to 6.23) respectively. Ongoing-pregnancy-rates and pregnancy-loss-rates per embryo-transfer-cycle were 27.3% vs. 24.4% vs. 32.5% (aOR=1.38, 95% CI=0.3-5.6, P=0.52), and 13.6% vs. 13.4% vs. 15.2%, (aOR=0.97, 95% CI=0.18-5.2, P=0.97) respectively. Cumulative-ongoing-pregnancy-rates per oocyte-retrieval-cycle were 36.5% vs. 34.5% vs. 35.5% (aOR=1.53, 95% CI=0.57 to 4.07, P=0.35). Median T(tr) was 146 days (IQR: 80-220). T(tr) negatively affected ongoing pregnancy rates for intervals <60 days (AUC=0.59, 95% CI=0.54-0.66, P<0.01). For T(tr) >60 vs. <60 days, the aOR for ongoing-pregnancy-per-embryo-transfer-cycle was 2.85 (95% CI=1.50-5.46, P<0.01). CONCLUSION: Covid-19 vaccination does not negatively influence embryological-outcomes or cumulative-ongoing-pregnancies after ART-treatments. Duration since vaccination may have a weak negative effect on embryo-transfer-outcomes performed within 60 days.

Luteal Phase Stimulation in the Same Cycle Is an Effective Strategy to Rescue POSEIDON Poor Responders with No Embryos after the First Follicular Stimulation.

Background: Poor responders may benefit from recruiting a 'second wave' of antral follicles within the same cycle. This concept forms the basis of double stimulation which has been named as 'DuoStim'. This protocol involves ovarian stimulation in both follicular and luteal phases with egg retrieval in each phase, respectively, to increase the number of oocytes and embryos in one menstrual cycle. This can be considered a potentially valuable option for women with poor ovarian reserve/response to maximise the number of oocytes retrieved in a single ovarian cycle in the shortest possible time. Aims: The aim of this study was to evaluate the efficacy of the DuoStim protocol in women classified as POSEIDON poor responders undergoing in vitro fertilization by comparing the embryological outcomes between the follicular and luteal phase stimulations in the same menstrual cycle. Settings and Design: This was a retrospective cohort study of 131 patients who enrolled to undergo DuoStim cycles from January 2021 to Sept. 2022, at a IVF center in a tertiary care hospital. Materials and Methods: The follicular phase stimulation used a standard antagonist protocol for the first oocyte retrieval. Thereafter, the luteal phase stimulation was started 3 days after the first retrieval, with the same dose of gonadotropin along with a daily 10 mg medroxyprogesterone acetate tablet, followed by a second oocyte retrieval. Blastocysts produced in both the phases were subsequently vitrified. Statistical Analysis Used: The paired t-test was used for comparing means and 95% confidence intervals (CIs) for different parameters. McNemar's test was used to compare paired proportions. The analysis was conducted using R statistical environment 4.2. Results: The mean number of oocytes retrieved and the mean number of utilizable blastocysts frozen per stimulation cycle were found to be significantly higher in the luteal phase as compared to the follicular phase (5.71 ± 3.95 vs. 4.87 ± 2.79, P = 0.02, and 1.43 ± 1.22 vs. 0.95 ± 1, P = 0.001, respectively). However, the mean fertilization rate and the mean blastocyst utilization rate were found to be similar between both the phases. The length of stimulation was found to be approximately 3 days longer in the luteal phase (12.63 ± 2.43 vs. 9.75 ± 1.85, P = 0.001). Overall, the odds of obtaining a usable blastocyst in the luteal phase was found to be significantly higher than in the paired follicular phase (73.9% vs. 57.7%, P = 0.012, odds ratio: 2.286 [95% CI: 1.186-4.636]). Also importantly, the luteal phase stimulation was able to rescue 68% (32/47) of patients where no blastocysts were formed in the follicular phase. Conclusion: Our data demonstrate that in women with poor reserve, the addition of luteal stimulation could increase the chances of achieving a pregnancy by significantly increasing the number of eggs and transferable embryos per menstrual cycle compared to follicular stimulation alone. Furthermore, luteal phase stimulation in the same cycle proved to be an effective strategy to rescue POSEIDON poor responders with no embryos after the first stimulation.

Low serum progesterone on day of transfer adversely impacts ongoing pregnancy rates in hormonally prepared single blastocyst frozen embryo transfer cycles.

OBJECTIVE: To evaluate if serum progesterone (P) levels on the day of transfer influence ongoing pregnancy rate (OPR) in hormonally prepared single blastocyst frozen embryo transfer (FET) cycles? STUDY DESIGN: Single center prospective cohort study conducted between June 2021 and August 2022 analyzed 217 single good quality blastocyst FET cycles hormonally prepared with oral estradiol valerate and micronized vaginal progesterone 400 mg twice daily. RESULTS: Mean serum P on the day of embryo transfer (ET) was 9.76 ± 5.19 ng/ml. Receiver operator curve (ROC) showed a significant predictive value of serum P levels on the day of ET for OPR, with an area under curve (AUC) (95 %CI) = 0.58 (0.49-0.66). Optimal serum P threshold for OPR was 7.7 ng/ml (Sensitivity 76.8%, Specificity 43.7%). 35.9% patients had serum P below this threshold. BMI was significantly higher (26.8 ± 3.7 vs 25.6 ± 4.3; p = 0.048) in patients with serum P < 7.7 ng/ml vs ≥ 7.7 ng/ml. OPR was significantly lower (24.4% vs 45.3%; p = 0.002) and clinical miscarriage rates significantly higher (37.9% vs 19.2%; p = 0.042) if serum P < 7.72 ng/ml vs ≥ 7.7 ng/ml. CONCLUSION: This study found that serum P level on the day of transfer in hormonally prepared FET cycles was a significant predictor of OPR.

Natural cycle versus hormone replacement cycle for transferring vitrified-warmed embryos in eumenorrhoeic women. A retrospective cohort study.

OBJECTIVE: To compare pregnancy, miscarriage and live birth rates and cycle monitoring parameters between Natural Cycle (NC-FET) and Hormone replacement cycle (HRC-FET) in eumenorrhoeic women undergoing vitrified-warmed autologous embryo transfer. STUDY DESIGN: Single-centre retrospective cohort study analyzed 173 NC-FET and 507 HRC-FET cycles with transfer of day2/3/5/6 embryos. Natural cycle monitoring occurred with serial ultrasound with the first day of the scan determined by the shortest cycle frequency. Serum progesterone was ordered when ultrasound was ambiguous in ascertaining ovulation. For HRC-FET oral estradiol valerate was used in fixed or escalating doses with maximum daily dose of 12 mg. Transdermal estradiol gel was added when desired endometrial thickness was not achieved. Vaginal progesterone was introduced with Endometrial thickness(ET)> = 7 mm. Embryos were transferred after stage-appropriate progesterone exposure. Luteal support was given with vaginal progesterone in NC-FET and vaginal and oral progesterone in HRC-FET. Primary outcome was live-birth-rate. Secondary outcomes were ET, length-of-estrogenic-phase, numbers-of-ultrasounds&hormone-monitoring, pregnancy&miscarriage rate. The odds ratio for live-birth was adjusted for age, embryo number, previous-live-births, previous-losses, past-negative-ET-cycles, IVF-indication and embryo-developmental-stage. Quantitative variables were compared using unpaired-t-test and qualitative variables with chi-square test. Two tailed p-value < 0.05 was considered significant. Binary logistic regression was used to calculate adjusted odds for live-births. RESULTS: The two cohorts were comparable in age, infertility-duration, previous-live-births, previous-losses, past-negative-ET-cycles, IVF-indication and embryo-developmental-stage. Length-of-estrogenic-phase was significantly shorter for NC-FET than HRC-FET 14.32 ± 2.83vs.18.18 ± 4.48; p = 0.0001) as was mean ultrasound-monitoring-scans (2.73 ± 0.95vs. 3.3 ± 1.04; p = 0.0001). Mean-endometrial-thickness (8.75 ± 1.83vs. 8.5 ± 1.25; p = 0.25) and mean-hormonal-tests (1.75 ± 1.28 vs. 1.88 ± 0.69; p = 0.09) did not differ significantly between NC-FET vs HRC-FET. Significantly higher live births took place in NC-FET vs. HRC-FET (87/173 = 50.3%vs.204/507 = 40.2%;p = 0.026). No significant difference was found in pregnancy rate (66.5% vs. 58%; p = 0.058) or in the pregnancy loss rate (24.3%vs30.6%; p = 0.23). The odds ratio for live-births adjusted for relevant variables was 1.48 (1.03-2.13) in NC-FET compared to HRC-FET. CONCLUSIONS: NC-FET is a superior method of endometrial preparation compared to HRC-FET in eumenorrhoeic women since it has a shorter estrogenic phase, reduces patient visits to the hospital and improves live birth rates. Future adequately powered studies should look at antenatal and perinatal outcomes, patient satisfaction rates and cost-effectiveness in the two endometrial preparation regimes.

Clomiphene based ovarian stimulation in a commercial donor program.

OBJECTIVE: This study was conducted to compare an extended clomiphene-based ovarian stimulation regimen with the conventional antagonist protocol in donor-recipient cycles. MATERIALS AND METHODS: A total of 170 (N) donors were stimulated between January 2013 and December 2013. Conventional antagonist protocol (group I) was employed in (n1 = 31) cycles, and clomiphene was used in (n2 = 139) donor cycles (group II). 50 mg clomiphene was given simultaneously with gonadotropins from day 2 of the cycle until the day of trigger. The analysis was performed retrospectively for oocytes retrieved, fertilization rates, cycle cancelation, blastocyst formation, and pregnancy rates. The dosages, cost, and terminal E2 (estradiol) were also compared between the two groups. RESULTS: The donor age groups were comparable in both the groups. There were no unsuccessful egg retrievals with clomiphene. The pregnancy rate (positive beta human chorionic gonadotropin) was significantly higher in the clomiphene group (odds ratio: 2.453; P = 0.02). Similarly, fertilization rate was significantly higher in the clomiphene group (59.5/50.5, P = 0.04). Eggs retrieved were similar in both groups, but the terminal E2 was significantly higher in the clomiphene group (P = 0.001). Average gonadotropin used was also significantly lower in clomiphene group (P < 0.001). CONCLUSION: Clomiphene can effectively prevent luteinizing hormone surge and limit the dose of gonadotropins thus bringing down the costs and its negative impact on the endometrium and oocyte quality.