Abdominal ectopic pregnancy following a frozen embryo transfer cycle: a case report

Background Abdominal ectopic pregnancy (AEP) is a rare form of ectopic pregnancy. As the number of in-vitro fertilization (IVF) procedures continues to increase, the incidence of AEP will also rise. However, the rarity and atypical presentation of AEP make early diagnosis challenging. Case presentation Herein, we report an AEP following frozen-thawed embryo transfer (FET) in an artificial cycle. The patient was misdiagnosed with implantation failure when the serum human chorionic gonadotropin (hCG) level was detected as 2.59mIU/ml at fourteenth day after embryo transfer. Therefore, she was suggested to stop luteal phase support. However, a ruptured AEP was developed 33 days following embryo transfer, which was diagnosed by laparoscopic surgery. Conclusions The case highlighted the delayed serum β-hCG and massive intraperitoneal hemorrhage may be clues to make early diagnosis of AEP. Clinicians must attach great importance to close monitoring and bear in mind the possibility of abdominal pregnancy.

The timing for initiating estrogen stimulation in artificial cycle for frozen-thawed embryo transfer can be flexible

Background There remains a lack of evidence to demonstrate whether the initiation time of estrogen stimulation is flexible in the proliferative endometrial phase during the artificial cycle for frozen-thawed embryo transfer (AC-FET). Methods FET records were retrospectively reviewed from a large university-affiliated reproductive medicine center. Only the patients who were undergoing their first embryo transfer with a single blastocyst in the AC-FET cycles were included: thereby 660 cycles were recruited, and the patients were grouped according to their day of estrogen usage initiation as early initiation group (estrogen stimulation initiated during days 2–5 of menses, n = 128) and the late initiation group (estrogen stimulation initiated on or after the 6th day of menses, n = 532). The primary outcome was the ongoing pregnancy rates (OPR). Results The rates of biochemical and clinical pregnancies were significantly higher in the late initiation group relative to those in the early initiation group, however, no significant differences were noted between the two groups for OPR. Furthermore, after adjusting for the results of the potential confounders, no impact was observed in the initiation time of estrogen stimulation on the OPR. Conclusions This study provides evidence that initiating the estrogen stimulation on after days 2–5 of menses do not exert adverse effects on the OPR in AC-FETs. Thus, AC-FET can be scheduled in a flexible manner without compromising on the pregnancy outcomes.

The Timing for Initiating Estrogen Stimulation in Artificial Cycle for Frozen-Thawed Embryo Transfer can be Flexible

Background: There remains a lack of evidence to demonstrate whether the initiation time of estrogen stimulation is flexible in the proliferative endometrial phase during the artificial cycle for frozen-thawed embryo transfer (AC-FET).Methods: FET records were retrospectively reviewed from a large university-affiliated reproductive medicine center. Only the patients who were undergoing their first embryo transfer with a single blastocyst in the AC-FET cycles were included: thereby 660 cycles were recruited, and the patients were grouped according to their day of estrogen usage initiation as early initiation group (estrogen stimulation initiated during days 2–5 of menses, n = 128) and the late initiation group (estrogen stimulation initiated on or after the sixth day of menses, n = 532). The primary outcome was the ongoing pregnancy rates (OPR). Results: The rates of biochemical and clinical pregnancies were significantly higher in the late initiation group relative to those in the early initiation group, however, no significant differences were noted between the 2 groups for OPR. Furthermore, after adjusting for the results of the potential confounders, no impact was observed in the initiation time of estrogen stimulation on the OPR.Conclusions: This study provides evidence that initiating the estrogen stimulation on after days 2–5 of menses do not exert adverse effects on the OPR in AC-FETs. Thus, FET can be scheduled in a flexible manner, according to the ovulatory and endometrial statuses and patient and/or clinic preference, without compromising on the clinical outcomes.

O-182 Higher risk of preeclampsia and pregnancy-induced hypertension with artificial cycle for Frozen-thawed Embryo Transfer compared to ovulatory cycle or fresh transfer following In Vitro Fertilization

Study question Is there an increased risk of preeclampsia after Frozen-thawed Embryo Transfer(FET) compared to In Vitro Fertilization-fresh transfer(IVF-fresh-ET) according to endometrial type of preparation for FET? Summary answer The frequency of preeclampsia and hypertension were significantly higher in the group of artificial cycle (AC-FET) compared to ovulatory cycle (OC-FET) and fresh-ET (P < 0.0001). What is known already Risks of maternal morbidity are known to be reduced in pregnancies resulting from FET compared to fresh-ET except for the risk of preeclampsia, that was reported to be significantly higher in pregnancies resulting from FET compared to fresh-ET or spontaneous conception. Most recent studies demonstrate an equal live birth rate with either OC-FET or AC-FET preparation. Few studies compared the maternal vascular morbidities with the two hormonal environments that preside over the early stages of embryonic development: OC (major role of the corpus luteum) and AC (prolonged hormone replacement with high doses of estrogen and progesterone). Study design, size, duration We conducted a 2013-2018 French nationwide cohort study comparing maternal vascular morbidities in 3 groups of single pregnancies> 22 weeks of gestation (WG): FET with AC or OC preparation, and IVF (conventional or ICSI)-fresh-ET.Data were extracted from the French National Health System database (>99% of national deliveries) in which all hospitalizations are registered, containing information on patient characteristics, diagnoses and treatments. Records were merged anonymously. Access to the database was legally approved. Participants/materials, setting, methods 68 025 deliveries were included: fresh-ET(n = 48 152), OC-FET(n = 9 500), AC-FET(n = 10 373). In OC-FET, a luteal phase support with progesterone was administered for maximum 6 WG if pregnancy. In AC-FET, progesterone was co-administered with estrogen until 12 WG. Embryos were transferred at cleavage or blastocyst stage. Vascular disorders were recorded if hospitalization for preeclampsia/eclampsia or hypertension (history of hypertension excluded). Maternal characteristics were included in multivariate analysis. Adjusted odds ratios(aOR) and 95% confidence intervals(CI) were estimated. Main results and the role of chance Maternal characteristics: In multivariate analysis, patients in the FET groups were older (33.4 years (std=4.3) vs. 33.2 years (std=4.4) for fresh-ET, respectively, P < 0.0001), less often primiparous (aOR=0.68[0.66-0.71], P < 0.0001) or smokers (aOR=0.84[0.75-0.95]) or with premature ovarian insufficiency (POI) (aOR=0.68 [0.58-0.79]), more frequently with polycystic ovaries (PCOS) (aOR=1.25[1.12-1.39]) and comparable for obesity or diabetes. In FET groups, 52.2% were AC-FET. There was no difference for maternal age, parity, obesity, smoking, history of diabetes between AC and OC-FET. Endometriosis (aOR=1.26[1.16-1.38]), PCOS (aOR=1.79[1.50-2.15]) and POI (aOR=2.0[1.48-2.72]) were more frequent in AC-FET. Risks of vascular disorders The rate of preeclampsia (5.3% vs. 2.3% vs. 2.4%, respectively, P < 0.0001) and hypertension (4.7% vs. 3.4% vs. 3.3%, respectively, P = 0.0002) was significantly higher in AC-FET versus OC-FET and fresh-ET. In multivariate analysis, the risk of preeclampsia increased with age, primiparity, obesity, diabetes and POI. The risk was higher in AC-FET versus OC-FET (aOR=2.42 [2.06-2.85]) and fresh-ET (aOR=2.43[2.2-2.7]), P < 0.00001. No difference was found between OC-FET and fresh-ET (P = 0.91). The risk of pregnancy-induced hypertension increased with age >40, primiparity, smoking, obesity and diabetes and was higher in AC-FET versus OC-FET (aOR=1.50[1.29-1.74], P < 0.0001) and fresh-ET (aOR=1.50[1.35-1.67], P < 0.0001) and not different between OC-FET and fresh-ET (P = 0.86). Limitations, reasons for caution While the strength of this study relies in the number and exhaustiveness of subjects analysed, its limitations are its retrospective and register-based nature that did not enable to refine the risk according to details of techniques and treatments in each group. Wider implications of the findings This large nationwide cohort study highlights 2 important information for physicians : i) the possible deleterious role of high supra-physiological and prolonged doses of estrogen-progesterone supplementation on vascular pathologies ii) the protective role of the corpus luteum present in stimulated or spontaneous OC for their prevention. Trial registration number Not applicable

P–654 What is the best luteal phase support in frozen-thawed embryo transfer cycle?

Study question What is the best progesterone administration for luteal phase support (LPS) in frozen-thawed embryo transfer cycle? Summary answer Different modes of hormonal luteal phase support do not affect clinical pregnancy rate (CPR) or live birth rate (LBR) in frozen-thawed embryo transfer (FET) cycles. What is known already FET has increased substantially over the last years. To support implantation, endometrial and embryo maturities must be synchronized; therefore, endometrial and follicular maturation are monitored either within the artificial cycle. Estrogen and progesterone are sequentially administered. The optimal endometrial preparation strategy remains unclear; this study aims to compare the reproductive and pregnancy outcomes between five different regimens of hormonal LPS for FET treatment. Study design, size, duration Single centre retrospective cohort study conducted between 2013 and 2019. Included were women (N = 402) aged 18–45 years undergoing FET. After an optimal endometrial preparation and endometrial thickness, the LPS was started. Thereafter, five different progesterone applications were compared: (1) oral dydrogesterone (10mg tid), (2) vaginal progesterone gel (90mg/d), (3) dydrogesterone (10mg tid) plus vaginal progesterone gel (90mg/d), (4) vaginal progesterone capsules (200mg tid), or (5) subcutaneous injection of 25mg daily. Participants/materials, setting, methods An ultrasound was performed 14 days of estrogene ( > =4mg/d) preparation. If the endometrial thickness was ≥7 mm and there was no dominant follicle, luteal support commenced four days before FET. Fourteen days after transformation, a serum beta-hCG test was performed. If positive (> 50 IU/L), a transvaginal ultrasound was performed to confirm clinical pregnancy, defined as gestational sac with fetal heart movement. CPR was assessed and delivery reports for LBR were collected later. Main results and the role of chance In total, 402 patients on an artificial cycle were included (mean age, 35 years (y); range, 26–46 y; standard deviation, 4.1 y). No differences in endometrial thickness and cause of infertility were found between groups. Multivariate logistic regression analysis revealed that the odds ratios (ORs) with 95% confidence intervals (CIs) for the CPR was significantly higher in the dydrogesterone only group (OR, 3.25; 95% CI, 1.7–6.2; p < 0.001) and in the combined group (3) (OR, 7.55; 95% CI, 2.7–21.10; p < 0.001). Statistically significant differences in live birth rate could not be found between the five groups; they were 33%, 54%, 8.3%, 4%, 0% for groups 1, 2, 3, 4, and 5 respectively. Overall satisfaction and tolerability were significantly higher in oral dydrogesterone compared to the vaginal progesterone. Limitations, reasons for caution This is a retrospective single-center study. Also, potentially confounding variables like ethnicity, parity, BMI were not accounted for, possibly contributing to bias. Further prospective randomized studies are needed. Wider implications of the findings: Oral dydrogesterone was found to be effective with equal CPR and LBR. Benefit is well-tolerated and accepted among patients; however we did not observe significant differences in the rates of live birth between the five regimens for used for LPS in women undergoing frozen-thawed embryo transfers. Trial registration number BASEC Switzerland 2020–01527

Increased Risk of High Birthweight in Singleton Newborns after Frozen-Thawed Embryo Transfer According to Endometrial Preparation, Ovulatory or Artificial Cycle

Background: It is unknown whether prolonged artificial hormonal environment during early fetal development affects the birthweight of singletons born after frozen-thawed embryo transfer (FET). Methods: A retrospective observational study included singleton births>22 weeks of gestation obtained after FET between 2013-2019 after endometrial preparation with ovulatory cycle (OC) or artificial cycle (AC). Our primary objective was to compare birthweight of singletons after FET between endometrial preparation by OC or AC. Secondary objectives included prolonged pregnancies, high birthweight, low birthweight, SGA and LGA rates. Multivariate analyses were performed considering potential confounding factors. Results: Among 198 singleton live births after FET, 112 were obtained with OC and 86 with AC. Prolonged pregnancies rate was higher in AC (25.6% vs. 7.1%, respectively, p=0.001). Mean birthweight was higher (+219g) in AC (3386g vs. 3167g, p=0.01; adjusted-p=0.052), as well as the rate of babies exceeding 4000g (16.3% vs. 2.7%, p=0.03, adjusted-p=0.015). The rate of babies <2500g was lower in AC (3.5% vs. 11.6%, respectively, p=0.050, adjusted-p=0.049). Conclusions: Since OC does not strain the chances of pregnancy and in the incomplete knowledge of the consequences of neonatal overweight on the future health of children, OC preparation could be advocated as first-line endometrial preparation in FET.