To evaluate the impact of serum LH levels prior to progestin administration on the outcomes of programmed frozen-thawed embryo transfer (FET) cycles.
Retrospective cohort study was conducted to compare the treatment outcomes between four groups based on the 25 percentiles of serum LH levels before progestin administration in 596 cycles of 518 patients undergoing artificial endometrial preparation protocols for FET. Primary outcome measures were ongoing and live birth rates. Secondary outcome measures were the pregnancy rates, clinical pregnancy rates, and pregnancy loss rates.
The trends in clinical pregnancy (CPR) and live birth rates (LBR) increased from the first to the fourth quartile (Q1 to Q4) of serum LH levels prior to progestin administration (37,0% to 48,3%, p = 0.042, and 22.6% to 39.5%, respectively, p = 0.003). Pregnancy loss rates (PLR) were higher in group Q1, although the difference was not statistically significant. Based on a multivariate logistic regression analysis, a low serum LH level before progestin initiation was found to be the most significant predictor associated with a negative effect on live birth (OR: 0,421, 95% CI 0,178 - 0,994, p=0,048). The day of estrogen initiation was significantly correlated with serum LH levels and quartiles of serum LH levels before progestin administration (r=0,200, p=0,015 and r=0,215, p=0,009, respectively).
The serum LH level prior to progestin administration significantly affects pregnancy and live birth rates in patients undergoing an artificial endometrial preparation protocol for FET. LH monitoring should be incorporated into the follow-up, in addition to assessing endometrial thickness and morphology in artificial FET cycles.

Superfetation is a very rare occurrence. In the context of assisted reproduction, it has been reported only as an intrauterine pregnancy after ovarian stimulation and/or embryo transfer in the presence of an undiagnosed ectopic pregnancy. Here we report a case of a 27-year-old anovulatory patient, gravida 1 para 1, who underwent two frozen-thawed single-blastocyst transfers in separate cycles. The patient reported that 12 days after the first transfer, she had menstrual bleeding and stopped her estradiol and progesterone supplementation without undergoing a blood human chorionic gonadotropin (βhCG) test. At her request, a second cycle was immediately initiated, with endometrial thickness measuring 4 mm. Eleven days after the second transfer, the βhCG value was inappropriately high. A right tubal pregnancy corresponding to 8 gestational weeks was diagnosed. Laparoscopy revealed a prominent right tubal pregnancy in addition to a significantly smaller left tubal pregnancy. The discordant tubal pregnancies were confirmed histologically. To our knowledge, superfetation involving a second ectopic pregnancy coexistent with a first, contralateral ectopic pregnancy consequent to consecutive in vitro fertilization procedures has not previously been described in the medical literature. This case emphasizes the importance of routine βhCG testing after every IVF cycle, even if apparently unsuccessful.

The administration of progesterone before transfer in hormone replacement treatment (HRT) is crucial for the clinical outcomes of frozen-thawed embryo transfer (FET), but the optimal duration of progesterone remains controversial. This study aimed to investigate the effect of the duration of progesterone administration on the clinical outcomes of FET cycles.
This prospective cohort study included 353 artificial FET cycles conducted at a reproductive medicine center between April and October 2021. The FET cycles were stratified into four groups based on the duration of progesterone supplementation before the procedure and the embryonic development stage: group P3 (73 patients) received intramuscular progesterone for 3 days and group P4 (87 patients) for 4 days before Day 3 frozen embryo transfer, group P5 (70 patients) for 5 days and group P6 (123 patients) for 6 days before frozen blastocyst transfer. This trial was performed using one or two vitrified embryo(s) when the endometrial thickness reached 7 mm after estrogen supplementation in an artificial cycle. The primary outcome was clinical pregnancy, and secondary outcomes included biochemical pregnancy, implantation, early pregnancy loss, and live births.
There were no significant differences in the demographic and clinical characteristics between the groups. No significant difference was observed in the clinical pregnancy rates between groups: 23/73 (31.5%) in group P3 vs 28/87 (32.2%) in group P4 (P = 0.927). Compared to group P5 (41/70, 58.6%), the clinical pregnancy rate was not significantly different in group P6 (77/123, 62.6%, P = 0.753). There was no significant difference in the implantation rates between groups: 33/136 (24.3%) in group P3 vs 34/166 (20.5%) in group P4 (P = 0.431), and 62/133 (46.6%) in group P5 vs 107/231 (46.3%) in group P6 (P = 0.956). The duration of progesterone supplementation (mean: 3.5 ± 0.5 days; range:3-4 days) before Day 3 frozen embryo transfer did not impact clinical pregnancy (odds ratio [OR] 1.048; 95% confidence interval [CI], 0.518-2.119). The duration of progesterone administration (mean: 5.6 ± 0.5 days; range:5-6 days) before frozen blastocyst transfer may not affect clinical pregnancy (OR 1.339; 95% CI, 0.717-2.497).
There may be no significant correlation between the duration of progesterone supplementation and pregnancy outcomes in artificial FET cycles, although the clinical pregnancy rate was higher when progesterone supplementation was extended for one day before FET.

To evaluate whether patients with high-serum progesterone levels before frozen embryo transfer (FET) under hormonal replacement therapy present with worse reproductive outcomes.
A cohort retrospective study.
A university-affiliated fertility center.
A total of 3,183 FET cycles in patients receiving hormonal replacement therapy between March 2009 and December 2020 were included. The luteal phase was covered with 200 mg per 8 hours of vaginal micronized progesterone either alone or in combination with a daily subcutaneous injection of 25 mg of progesterone. A total of 1,360 cycles corresponded to frozen homologous embryo transfer (ET) (hom-FET), 1,024 were euploid ET (eu-FET) after preimplantation genetic testing for aneuploidies, and 799 cycles were frozen heterologous ET (het-FET). All patients had adequate serum progesterone levels (≥10.6 ng/mL) before the procedure.
Frozen embryo transfer cycles.
Clinical pregnancy, miscarriage, and live birth rates (LBRs).
Median (P25; P75) serum progesterone level before FET was 14.39 (12.43-17.49) ng/mL. Progesterone levels were significantly higher in the group under vaginal plus subcutaneous progesterone (15.96 [13.74-21.60] vs. 14.09 [12.19-16.95]). No differences in clinical pregnancy, miscarriage, and LBR were observed based on the use of vaginal or vaginal plus subcutaneous progesterone for each of the groups (hom-FET, eu-FET, and het-FET). Live birth rates were comparable among patients in the highest centile of serum progesterone levels (≥p90) (22.33 ng/mL) and the rest of the patients (p<90) (43.9% vs. 41.3%). Patients with progesterone levels ≥p90 presented lower body mass index than those in the lower centiles (Elevated serum progesterone levels before FET do not impair reproductive outcomes in patients receiving artificially prepared cycles with vaginal or vaginal plus subcutaneous progesterone.

Is there an association between serum LH levels prior to progesterone administration and live birth rate (LBR) in artificial frozen-thawed embryo transfer (FET) cycles?
: Low serum LH levels on the day before progesterone initiation in artificial frozen-thawed blastocyst transfer cycles of ovulatory women are associated with a lower LBR.
In artificial FET cycles, exogenous oestrogen and progesterone are administered sequentially to mimic the serum hormone pattern similar to the natural cycle. In oestrogen-only phase, the supplemental oestrogen causes thickening of the endometrium and is sometimes accompanied by a rise in serum LH. However, whether the endogenous LH level in artificial FET cycles is related to clinical outcomes remains unclear.
A retrospective cohort study including 3469 artificial frozen-thawed blastocyst transfer cycles was conducted at a tertiary-care academic medical centre between February 2014 and January 2020.
A total of 3469 frozen blastocyst transfer cycles were stratified into four groups based on the quartiles of serum LH level before progesterone initiation: <25th percentile (LH < 8.79 mIU/ml), 25-50th percentile (8.79 ≤ LH ≤ 13.91 mIU/ml), 51-75th percentile (13.91 < LH ≤ 20.75 mIU/ml) and >75th percentile (LH > 20.75 mIU/ml). The serum LH level >75th percentile group was considered as the reference group. Patients with polycystic ovarian syndrome or other ovulatory disorders were excluded from the study. We also excluded cycles with an endometrial thickness <7 mm before progesterone initiation and patients with intrauterine adhesions and uterine abnormalities. In order to avoid the interference of BMI, all patients were divided into two categories based on the overweight threshold: BMI <25 kg/m2 and ≥25 kg/m2, and the impacts of serum LH levels on LBR were investigated separately. Univariable and multivariable logistic regression analysis were performed to adjust for potential confounders. EmpowerStats software and R-project were used to build smooth curve fitting models.
Compared with the reference group, the implantation rate significantly decreased with low LH levels (<25th percentile) on the day before progesterone initiation (odds ratio [OR] = 0.74; 95% CI, 0.64-0.86; P = 0.001). Accounting for major covariates, low LH levels were associated with a relatively lower LBR (adjusted OR = 0.649; 95% CI, 0.531-0.794; P < 0.001), mainly due to a lower implantation rate, lower clinical pregnancy rate and higher pregnancy loss rate. Moreover, in the patients with BMI <25 kg/m2, low LH was associated with a lower LBR (P < 0.001); while in the overweight subgroup, LBR and LH were not correlated (P = 0.823).
The main limitation of this study is its retrospective design. Owing to the relatively small number in the overweight group, the results of the overweight subgroup should be interpreted with caution.
The evidence provided in this study shows the importance of serum LH levels on the day before progesterone initiation in patients undergoing artificial FET cycles. Hypothalamic dysfunction may be one of the important causes of a relatively low LH, which is related to impaired pregnancy outcomes. Serum LH levels may be used as one of the clinical indicators to predict pregnancy outcomes.
No funding and no competing interest were involved in this study.
NA.

OBJECTIVE: To study whether serum estradiol (E2) levels prior to progesterone administration in the artificial endometrial preparation (AEP) of frozen-thawed blastocyst transfer affect the live birth rate.
METHODS: Retrospective cohort study.
METHODS: Tertiary-care academic medical centre.
METHODS: A total of 3857 frozen-thawed blastocyst transfer cycles were divided into three groups: <200 pg/ml (n = 1676); 200-399 pg/ml (n = 1296); and ≥400 pg/ml (n = 885), based on the 25th (182.3 pg/ml) and 75th percentile (390.2 pg/ml) of serum E2 level prior to progesterone administration.
METHODS: Univariable and multivariable logistic regression analysis was performed.
METHODS: The primary outcome of the study was the live birth rate and the secondary outcomes included clinical pregnancy rate, pregnancy loss rate, neonatal birthweight, Z-score, and small for gestational age (SGA).
RESULTS: Compared with the reference group, accounting for major covariates, the live birth rate significantly decreased in the \'≥400 pg/ml\' group (adjusted OR 0.71, 95% CI 0.59-0.85). Compared with the reference group, there was an association between the E2 level in the \'≥400 pg/ml\' group and a decrease in the clinical pregnancy rate (adjusted OR 0.74, 95% CI 0.61-0.89). Compared with the reference group, the pregnancy loss rate significantly increased in the \'≥400 pg/ml\' group (adjusted OR 1.45, 95% CI 1.08-1.93). The E2 levels did not affect neonatal birthweight, Z-score, and SGA among singletons.
CONCLUSIONS: High serum E2 levels prior to progesterone administration in AEP are associated with a decreased live birth rate after frozen-thawed blastocyst transfer.
UNASSIGNED: High serum E2 levels prior to progesterone administration in artificial FET are associated with a decreased live birth rate after frozen-thawed blastocyst transfer.