Optimizing estradiol level for gonadotrophin-releasing hormone antagonist initiation among patients with simple tubal factor infertility.

Objective: The aim of this study is to investigate the optimal estradiol (E2) level on the day of gonadotropin-releasing hormone antagonist (GnRH-ant) initiation to maximize the clinical pregnancy rate (CPR) after fresh embryo transfer among patients with simple tubal factor infertility. Methods: A retrospective cohort study was conducted in the Reproductive Medicine Center, the Second Hospital of Hebei Medical University. A total of 1,493 IVF-ET cycles of patients diagnosed with single tubal factor infertility from August 2016 to August 2021 were included and equally allocated into five distinct groups according to the quintile serum E2 levels on the day of GnRH-ant initiation. The five groups had similar baseline data except for antral follicle count. Results: The serum E 2 level on GnRH-ant initiation day was determined as an independent predictor of clinical pregnancy after adjusting for confounding factors such as age, infertility duration, body mass index, cycle number, antral follicle count, and the number of transferred embryos. Through smooth curve fitting, we found that, with the increase of serum E2 levels on the day of GnRH-ant initiation, CPR showed a trend of slight increase and then slight decrease. The maximal CPR was achieved when the serum E2 level on GnRH-ant initiation day was 498 pg/ml. When E2 was less than 498 pg/ml, the odds ratio (OR) of clinical pregnancy was 1.05 (95% CI: 1.00, 1.11, P = 0.0583). When E2 was greater than 498 pg/ml, the OR of clinical pregnancy was 0.97 (95% CI: 0.95, 0.98, P = 0.0003). Furthermore, CPR remained high when E2 was 436.8-658.6 pg/ml but declined significantly by more than 40% when E2 was ≥ 894.4 pg/ml (P < 0.05). Conclusions: The serum E2 level should be considered as an adjuvant parameter for GnRH-ant initiation. The best E2 value was 498 pg/ml, and GnRH-ant administration could be recommended to initiate when serum E2 was 436.8-658.6 pg/ml. If GnRH-ant was initiated when serum E2 was above 894.4 pg/ml, then the CPR after fresh embryo transfer may decline dramatically, and thus, cancellation of fresh embryo transfer and earlier initiation of GnRH-ant in future cycles should be considered.

Factors affecting clinical pregnancy in controlled ovarian hyperstimulation with GnRH-a long protocol: a retrospective cross-sectional study.

This retrospective cross-sectional study was to investigate factors affecting clinical pregnancy in patients who received gonadotropin-releasing hormone agonist luteal phase long protocol (GnRH-a long protocol) and underwent fresh in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer cycle. One thousand five hundred and twenty-five patients who received GnRH-a long protocol and underwent fresh IVF/ICSI embryo transfer cycle were enrolled. The clinical pregnancy rate (63.1 vs. 22.4%, p < .05) and live birth rate (53.8 vs. 14.5%, p < .05) were significantly higher while the miscarriage rate (12.5 vs. 35.3%, p < .05) was significantly lower in the two embryo group than those in the one embryo group. The clinical pregnancy rate (48.5 vs. 64.1%, p < .05) and live birth rate (38.4 vs. 55.0%, p < .05) were significantly lower in patients older than 33.5 years than those in younger patients. The clinical pregnancy rate (52 and 60.6 vs. 79.7%, p < .05) and live birth rate (36 and 51.4 vs. 69.6%, p < .05) of the thin and mediate groups were significantly lower than those in the thick group, whereas the ectopic pregnancy rate (11.5 and 1.9 vs. 0%, p < .05) was significantly higher in the thin group than in the mediate and thick group. Multivariate logistic regression analysis showed that age (OR = 0.956, 95% CI [0.931, 0.982], p < .05), number of embryos transferred (OR = 2.491, 95% CI [1.670, 3.715], p < .05) and endometrial thickness on the transplantation day (OR = 1.124, 95% CI [1.067, 1.185], p < .05) were independent factors significantly associated with clinical pregnancy. In conclusion, endometrial thickness (>14.69 mm) on the day of transfer, two cleavage embryos transferred, and female age (≤33.5 years) are independent factors affecting clinical pregnancy outcomes in controlled ovarian hyperstimulation with GnRH-a long protocol for assisted conception. IMPACT STATEMENTWhat is already known on this subject? Fresh embryo transfer cycle with GnRH-a long protocol will result in a higher pregnancy rate in controlled ovarian hyperstimulation cycles.What do the results of this study add? Endometrial thickness on the day of transfer, number of embryos transferred, and female age were independent factors affecting clinical pregnancy outcomes.What are the implications of these findings for clinical practice and/or further research? When performing a fresh IVF/ICSI embryo transfer cycle with GnRH-a long protocol for ovulation induction, the independent affecting factors should be taken into consideration.

Effect of Endometrium Thickness on Clinical Outcomes in Luteal Phase Short-Acting GnRH-a Long Protocol and GnRH-Ant Protocol.

Objective: To investigate the factors that influence luteal phase short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol and GnRH-antagonist (GnRH-ant) protocol on pregnancy outcome and quantify the influence. About the statistical analysis, it is not correct for the number of gravidities. Methods: Infertile patients (n = 4,631) with fresh in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transfer were divided into GnRH-a long protocol (n =3,104) and GnRH-ant (n =1,527) protocol groups and subgroups G1 (EMT ≤7mm), G2 (7 mm 10 mm) according to EMT on the trigger day. The data were analyzed. Results: The GnRH-ant and the GnRH-a long protocols had comparable clinical outcomes in the clinical pregnancy, live birth, and miscarriage rate after propensity score matching. In the medium endometrial thickness of 7-10 mm, the clinical pregnancy rate (61.81 vs 55.58%, P < 0.05) and miscarriage rate (19.43 vs 12.83%, P < 0.05) of the GnRH-ant regime were significantly higher than those of the GnRH-a regime. The EMT threshold for clinical pregnancy rate in the GnRH-ant group was 12 mm, with the maximal clinical pregnancy rate of less than 75% and the maximal live birth rate of 70%. In the GnRH-a long protocol, the optimal range of EMT was >10 mm for the clinical pregnancy rate and >9.5 mm for the live birth rate for favorable clinical outcomes, and the clinical pregnancy and live birth rates increased linearly with increase of EMT. In the GnRH-ant protocol, the EMT thresholds were 9-6 mm for the clinical pregnancy rate and 9.5-15.5 mm for the live birth rate. Conclusions: The GnRH-ant protocol has better clinical pregnancy outcomes when the endometrial thickness is in the medium thickness range of 7-10 mm. The optimal threshold interval for better clinical pregnancy outcomes of the GnRH-ant protocol is significantly narrower than that of the GnRH-a protocol. When the endometrial thickness exceeds 12 mm, the clinical pregnancy rate and live birth rate of the GnRH-ant protocol show a significant downward trend, probably indicating some negative effects of GnRH-ant on the endometrial receptivity to cause a decrease of the clinical pregnancy rate and live birth rate if the endometrial thickness exceeds 12 mm.

Effects of age on pregnancy outcomes in patients with simple tubal factor infertility receiving frozen-thawed embryo transfer.

This study was to retrospectively analyze the effect of the age of embryos transfer and oocyte retrieval on the clinical pregnancy outcome in patients with simple tubal factor infertility (TFI) who received frozen-thawed embryo transfer. Patients (n = 3619) with simple TFI who underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) frozen-thawed embryo transfer at our hospital were enrolled. Univariate logistic regression analysis, categorical multivariate logistic regression analysis, curve fitting and threshold effect analysis were performed. Age of embryo transfer was a significant (P < 0.05) independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rates. The Clinical pregnancy outcome declined significantly after the age of 34 years. After limiting the female oocyte retrieval age to ≤ 34 years, no significant change was detected in the clinical pregnancy, live birth, or miscarriage rate with increase of transplantation age. In conclusion, in patients with simple TFI undergoing IVF/ICSI frozen-thawed embryo transfer, age is a significant independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rate. Aging of oocytes has a greater impact on the clinical pregnancy in women with simple TFI than the aging of the body. Patients with TFI can freeze embryos in advance to preserve fertility.

Effects of intramuscular and vaginal progesterone supplementation on frozen-thawed embryo transfer.

This study was to investigate effects of progesterone vaginal sustained-release gel and intramuscular injection of progesterone on frozen-thawed embryos transfer in 3013 patients receiving vaginal progesterone sustained-release gel and progesterone injection in artificial cycle for frozen-thawed embryo transfer. All patients were divided into two groups: group A with progesterone intramuscular injection (60 mg/d) plus dydrogesterone (10 mg tid) and group B with progesterone vaginal sustained-release gel of progesterone (90 mg/d) plus dydrogesterone (10 mg tid). There were 1988 women in group A treated with progesterone injection and 1025 women in group B with progesterone vaginal sustained-release gel. There were no statistically (P > 0.05) significant difference between the two groups in age, years of infertility, body mass index, endometrial thickness at transfer time, the average numbers of embryo transferred, cause of infertility, number of cycles, pregnancy rate and ectopic pregnancy rate. No significant (P > 0.05) differences existed in the clinical pregnancy (52.5% vs. 56.0%) and ectopic pregnancy (2.2% vs. 3.0%) rate between groups A and B. However, group B with vaginal progesterone supplementation had significantly (P < 0.05) greater implantation (37.0% vs 34.4%), delivery (45.1% vs. 41.0%) and live birth (45.0% vs. 40.8%) rate than group A with intramuscular progesterone injection, whereas group A had significantly (P < 0.05) greater early abortion rate (19.4% vs. 15.3%) than group B. This study showed that vaginal gel progesterone supplementation has good effects on frozen-thawed embryo transfer and can significantly increase the rate of implantation, delivery and live birth but decrease the abortion rate compared with intramuscular progesterone injection.