Dataset Information

Perinatal outcomes of neonates born from different endometrial preparation protocols after frozen embryo transfer: a retrospective cohort study.

ABSTRACT:

Background

Previous studies have focused on pregnancy outcomes after frozen embryo transfer (FET) performed using different endometrial preparation protocols. Few studies have evaluated the effect of endometrial preparation on pregnancy-related complications. This study was designed to explore the association between different endometrial preparation protocols and adverse obstetric and perinatal complications after FET.

Methods

We retrospectively included all FET cycles (n = 12,950) in our hospital between 2010 and 2017, and categorized them into three groups, natural cycles (NC), hormone replacement therapy (HRT) and ovarian stimulation (OS) protocols. Pregnancy-related complications and subsequent neonatal outcomes were compared among groups.

Results

Among all 12,950 FET cycles, the live birth rate was slightly lower for HRT cycles than for NC (HRT vs. NC: 28.15% vs. 31.16%, p < 0.001). The pregnancy loss rate was significantly higher in OS or HRT cycles than in NC (HRT vs. NC: 17.14% vs. 10.89%, p < 0.001; OS vs. NC: 16.44% vs. 10.89%, p = 0.001). Among 3864 women with live birth, preparing the endometrium using OS or HRT protocols increased the risk of preeclampsia, and intrahepatic cholestasis of pregnancy (ICP) in both singleton and multiple deliveries. Additionally, OS and HRT protocols increased the risk of low birth weight (LBW) and small for gestational age (SGA) in both singletons and multiples after FET.

Conclusion

Compared with HRT or OS protocols, preparing the endometrium with NC was associated with the decreased risk of pregnancy-related complications, as well as the decreased risk of LBW and SGA after FET.

SUBMITTER: Li C

PROVIDER: S-EPMC8086106 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The optimal protocol for endometrial preparation in patients with infertility remains unclear. Due to this, the current study retrospectively analyzed 1,589 patients with infertility and regular menstrual cycles to assess reproductive outcomes per embryo transferred and per embryo transfer (ET) cycle following the transfer of frozen-thawed embryos (FET) in a modified natural cycle (mNC) or hormone therapy cycle (HT) with or without gonadotropin-releasing hormone agonist (GnRHa)-induced pituitary suppression. The molecular mechanisms involved were also studied using tissues from endometrial biopsies. Patients who underwent FET were assigned to 5 groups as follows: Group A underwent a mNC (n=276); group B (n=338) received estradiol (E2) and progesterone (P4); group C received 1 cycle of GnRHa, E2 and P4 (n=323); group D received 2 cycles of GnRHa, E2 and P4 (n=329); and group E received 3 cycles of GnRHa, E2 and P4 (n=323). Tissues from endometrial biopsies of 91 patients performed on the day of ET were tested for endometrial receptivity marker mRNA expression and microRNA (miR)-223-3p mRNA. Furthermore, endometrial stromal cells (ESCs) were used for an in-depth study of the molecular mechanisms involved. Among the 5 groups of patients, implantation rates, clinical pregnancy rates and live birth rates were not significantly different. However, endometrial receptivity was enhanced in group E when compared with groups A-D, which was associated with endometrial leukemia inhibitory factor (LIF), osteopontin, vascular endothelial growth factor, integrin ?3 and homeobox gene 10 and 11 mRNA upregulation, and miR-223-3p miRNA downregulation. Transfection of ESCs with an miR-223-3p mimic significantly reduced levels of LIF mRNA and protein. In addition, pre-treating ESCs with GnRHa upregulated mRNA and protein expression of the decidualization markers prolactin and insulin-like growth factor binding protein-1 in a time-dependent manner. In conclusion, these results indicated that HT with GnRHa may be a potential endometrial preparation protocol for FET.

Project description:BackgroundLow serum progesterone on the day of frozen embryo transfer (FET) is associated with diminished pregnancy rates in artificial endometrium preparation cycles, but there is no consensus on whether strengthened luteal phase support (LPS) benefits patients with low progesterone on the FET day in artificial cycles. This single-centre, large-sample retrospective trial was designed to investigate the contribution of strengthened LPS to pregnancy outcomes for groups with low progesterone levels on the FET day in artificial endometrium preparation cycles.MethodsWomen who had undergone the first artificial endometrium preparation cycle after a freeze-all protocol in our clinic from 2016 to 2018 were classified into two groups depending on their serum progesterone levels on the FET day. Routine LPS was administered to group B (P ≥ 10.0 ng/ml on the FET day, n = 1261), and strengthened LPS (routine LPS+ im P 40 mg daily) was administered to group A (P < 10.0 ng/ml on the FET day, n = 1295). The primary endpoint was the live birth rate, and the secondary endpoints were clinical pregnancy, miscarriage and neonatal outcomes.ResultsThe results showed that the clinical pregnancy rate was significantly lower in group A than in group B (48.4% vs 53.2%, adjusted risk ratio (aRR) 0.81, 95% confidence interval (CI) 0.68, 0.96), whereas miscarriage rates were similar between the two groups (16.0% vs 14.7%, aRR 1.09, 95% CI 0.77, 1.54). The live birth rate was slightly lower in group A than in group B (39.5% vs 43.3%, aRR 0.84, 95% CI 0.70, 1.0). Birthweights and other neonatal outcomes were similar between the two groups (P > 0.05).ConclusionsThe results indicated that the serum progesterone level on the FET day was one of the risk factors predicting the chances of pregnancy in artificial endometrium preparation cycles, and strengthened LPS in patients with low progesterone on the FET day might help to provide a reasonable pregnancy outcome in artificial cycles, although further prospective evidence is needed to confirm this possibility.

Project description:BackgroupFrozen-thawed embryo transfer is rising worldwide. One adverse effect of programmed frozen embryo transfer (FET) reported in some studies is an increased risk of adverse obstetric and perinatal outcomes. Meanwhile, body mass index (BMI) also has adverse effect on obstetric and perinatal outcomes. In this study, we investigated that the influence of different endometrial preparation protocols on obstetric and perinatal outcomes and the role of BMI in it.MethodThis retrospective cohort study included 2333 singleton deliveries after frozen-thaw embryo transfer at our centre between 2014 and 2021, including 550 cycles with programmed FET, 1783 cycles with true natural cycle FET (tNC-FET). In further analysis according to BMI grouped by Asian criterion, group A (18.5 kg/m2 ≤ BMI < 24.00 kg/m2) included 1257 subjects, group B (24 kg/m2 ≤ BMI < 28.00 kg/m2) included 503 subjects and group C (BMI ≥ 28 kg/m2) included 573 subjects. Baseline characteristics of the two groups were compared and analyzed. Binary logistic regression analyses were performed to explore the association between obstetric and perinatal outcomes and endometrial preparation protocols.ResultsThere were no significant differences in the placenta previa, gestational diabetes mellitus(GDM), preterm premature rupture of membranes (PPROM), cesarean section (CS) and macrosomia between the tNC-FET and programmed FET groups (P > 0.05). The programmed FET cycles were associated to a higher risk of pregnancy-induced hypertension (PIH) compared with the tNC-FET cycles (7.3% vs 4.4%, crude OR 1.71[1.16-2.54]; adjusted OR 1.845[1.03-3.30]). After dividing the patients into three groups according to the BMI, The programmed FET cycles were associated to a higher risk of PIH in group C (14.4% vs 6.2%, crude OR 2.55 [1.42-4.55]; adjusted OR 4.71 [1.77-12.55]) compared with the tNC-FET cycles. But there was no statistically significant difference in group A and group B. Programmed FET group compared with the tNC-FET group, the risk of PIH increase as the body mass index increase.ConclusionThis study showed a tendency toward increasing risk of PIH in programmed FET cycle compared with the tNC-FET cycle, and the risk of PIH increases as BMI increases. Increased risk of preterm birth and low birth weight is linked to increased risk of PIH.

Project description:Study questionAre there growth differences between singleton children born after frozen embryo transfer (FET), fresh embryo transfer (ET), and natural conception (NC)?Summary answerAdolescent boys born after FET have a higher mean proportion and increased odds of overweight compared to those born after fresh ET.What is known alreadyChildren born after FET have higher mean birthweights and an increased risk of large-for-gestational-age compared to those born after fresh ET and even NC. This raises questions about possible growth differences later in childhood. Previous studies on child growth after FET report partly conflicting results and lack long-term data until adolescence.Study design, size, durationThis was a cohort study based on national population-based registers, the Finnish Medical Birth Register and the Register of Primary Health Care visits, including singletons born after FET (n = 1825), fresh ET (n = 2933), and NC (n = 31 136) in Finland between the years 1995 and 2006.Participants/materials, setting, methodsThe proportions of overweight (i.e. age- and sex-adjusted ISO-BMI for children ≥ 25) were compared between the groups. Odds ratios (ORs) and adjusted odds ratios (aORs) of overweight were calculated. Adjustments were made for birth year, preterm birth, maternal age, parity, and socioeconomic status. Mean heights, weights, and BMIs were compared between the groups each year between the ages of 7 and 18.Main results and the role of chanceFET boys had a higher mean proportion of overweight (28%) compared to fresh ET (22%, P < 0.001) and NC (26%, P = 0.014) boys. For all ages combined, the aOR of overweight was increased (1.14, 95% CI 1.02-1.27) for FET boys compared to fresh ET boys. For girls, the mean proportions of overweight were 18%, 19%, and 22% for those born after FET, fresh ET, and NC, respectively (P = 0.169 for FET vs fresh ET, P < 0.001 for FET vs NC). For all ages combined, FET girls had a decreased aOR of overweight (0.89, 95% CI 0.80-0.99) compared to NC girls. Growth measurements were available for 6.9% to 30.6% of FET boys and for 4.7% to 29.4% of FET girls at different ages.Limitations, reasons for cautionUnfortunately, we were not able to adjust for parental anthropometric characteristics. The growth data were not available for the whole cohort, and the proportion of children with available measurements was limited at the start and end of the follow-up. During the study period, mainly cleavage stage embryos were transferred, and slow freezing was used for ART.Wider implications of the findingsThe risk of overweight among FET boys warrants further research. Future studies should aim to investigate the mechanisms that explain this sex-specific finding and combine growth data with long-term health data to explore the possible risks of overweight and cardiometabolic disease in adulthood.Study funding/competing interest(s)Funding was obtained from the Päivikki and Sakari Sohlberg Foundation, the Alma and K.A. Snellman Foundation (personal grants to A.M.T.), and the Finnish Government Research Funding. The funding sources were not involved in the planning or execution of the study. The authors declare no conflicts of interest.Trial registration numberN/A.

Project description:Background:Extended embryo culture has been reported to affect perinatal outcome regarding higher risks of large for gestational age (LGA) and preterm birth (PTB) yet decreased risk of small for gestational age (SGA). However, existing data about the obstetric outcome and the safety for offspring resulting from the transfer of day 7 blastocysts is rare. Objectives:To compare obstetric and perinatal outcome using embryos vitrified on day 7 with those vitrified on day 3, day 5, and day 6. Methods:Data were collected from 4489 infertile women who gave birth to live-born singletons after vitrified-warmed embryo transfer cycles from January 1, 2006 to December 31, 2017. Singletons were compared depending on the age of embryos. Main perinatal outcome parameters included PTB (gestational age < 37 weeks), very PTB (VPTB, gestational age < 32 weeks), LGA (birthweights > 90th percentiles), and SGA (birthweights < 10th percentiles). Obstetric outcomes included gestational diabetes (GDM), pregnancy-induced hypertension (PIH), preterm premature rupture of membranes (PPROM), pre-eclampsia, placenta previa, placental abruption, and postpartum hemorrhage. Propensity score matching (PSM) was used to adjust the confounding factors across groups and then analyze the association between in vitro culture period and the outcome measures. Results:After PSM, the transfer of day 7 blastocysts was associated with higher birth weight Z-scores and increased incidence of very large for gestational age (VLGA) compared with the transfer of day 3 cleavage-stage embryos while the incidence of PTB, low birth weight (LBW), SGA did not reach statistical significance. Moreover, comparable perinatal outcome was found in the comparison of day 7 vs. day 5 and day 7 vs. day 6. Day 7 blastocysts did not result in adverse obstetric outcome compared with day 3, day 5, and day 6 embryos, respectively. Conclusion:In vitrified-warmed transfer cycles, day 7 blastocysts were associated with adverse perinatal outcome regarding higher risk of VLGA compared with day 3 cleavage-stage embryo, while blastocysts with diverse growth rates embrace similar developmental viability regardless of blastocysts vitrified on day 5, day 6, or day 7.