In Vitro Fertilization Pregnancies Research Articles

Sleep quality is associated with the weight of newborns after in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI).

Sleep disorders are thought to be common in women with in vitro fertilization and embryo transfer (IVF-ET) conception. Although a few studies have investigated the association between maternal sleep quality and infant birth weight, it is unclear to what extent birth weight is associated with sleep quality during pregnancy among these women. Therefore, we conducted a cohort study to assess sleep quality among women receiving IVF-ET during the subsequent pregnancy and investigated the association of self-report sleep quality on infant birth weight. This study was a prospective cohort study recruiting women who were to receive assisted reproductive technology (ART). Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI) before oocyte retrieval and in the first trimester, second trimester, and third trimester during pregnancy. A generalized estimating equation (GEE) model was applied to evaluate the associations between sleep quality at specific times and infant birth weight. A general linear model was conducted to explore which component of the PSQI questionnaire was most associated with infant birth weight. Between August 2016and August 2020, a total of 1344 womenwho had singleton births with IVF conception were included in the analysis. PSQI scores in the first trimester were highest (4.59 ± 2.47) but had no significant relationship with birth weight. After accounting for potential influencing factors, we found that poor maternal sleep quality in the second trimester was significantly associated with small for gestational age (SGA) among female infants (OR = 3.03, 95% CI = 1.04 to 9.71, P = 0.044), while no association was observed between sleep quality and birth weight in male infants (OR = 1.64, 95% CI = 0.68 to 3.99, P = 0.271). These findings suggest that the sleep quality of women with IVF pregnancies may influence fetal weight in a trimester- and sex-specific manner.

Multifoetal gestations mediate the effect of in vitro fertilisation (IVF) on ischaemic placental disease in autologous oocyte IVF more than donor oocyte IVF.

Ischaemic placental disease (IPD) affects 16%-23% of pregnancies in the United States. In vitro fertilisation (IVF) is a risk factor for IPD, and the magnitude of increase in risk differs for individuals using donor oocytes (donor IVF) versus their own oocytes (autologous IVF). In addition, multifoetal gestations, which are more common in IVF than non-IVF pregnancies, also are a risk factor for IPD. To quantify the contribution of multifoetal gestations to the association between IVF and IPD. We conducted a retrospective cohort study at a tertiary hospital from 1January, 2000 to 1 August 2018 using electronic medical records and state vital statistics data. IPD was defined as preeclampsia, placental abruption, small for gestational age (SGA) birth or an intrauterine foetal demise due to placental insufficiency. We used mediation analysis to decompose the total effect of IVF on IPD into a natural direct effect and an indirect effect through multifoetal gestations. We repeated the analyses separately for donor and autologous IVF. All models were adjusted for maternal age, race, parity, insurance, year of delivery and account for multiple pregnancies per person. We identified 86,514 deliveries, of which 281 resulted from donor IVF and 4173 resulted from autologous IVF. IVF pregnancies had 1.99 (95% CI 1.88, 2.10) times the risk of IPD compared to non-IVF pregnancies, and 75.5% of this increased risk was mediated by multifoetal gestations. Autologous IVF pregnancies had 1.95 (95% CI 1.84, 2.07) times the risk of IPD compared to non-IVF pregnancies, and the per cent mediated was 78.8%. Donor IVF pregnancies had 2.50 (95% CI 2.09, 2.92) times the risk of IPD, but the per cent mediated was 37.5%. The majority of the association between autologous IVF and IPD was mediated through multifoetal gestations; however, this was not the case for donor IVF pregnancies.

Gestational diabetes mellitus in in-vitro fertilization pregnancies – Clinical and placental histological characteristics

We aimed to investigate obstetric and neonatal outcomes and placental histological findings in in vitro fertilization (IVF) pregnancies complicated by gestational diabetes mellitus (GDM) as compared to unassisted pregnancies. This was a retrospective cohort of deliveries at a single university affiliated center between 12/2008 and 01/2020. Included were singleton pregnancies complicated by GDM, for which placental histopathological examination was performed. Obstetric, neonatal and placental outcomes were compared between pregnancies following IVF and unassisted pregnancies. Placental lesions were categorized according to the "Amsterdam" criteria. Included were 688 deliveries with a diagnosis of GDM with placental examination - 69 IVF pregnancies (IVF group) and 619 unassisted pregnancies (control group). The IVF group was characterized by a significantly higher maternal age and higher rate of nulliparous women - 60.8% vs. 32.9%, p<0.001. There were no differences in GDM type between the study groups - about two thirds of cases were GDMA1 and on third GDMA2. A higher incidence of preeclampsia was noted in the IVF group - 17.3% vs. 9.3%, p=0.03, with no difference in cesarean deliveries and birthweight. IVF deliveries were characterized by a significantly higher rate of adverse neonatal outcomes - 18.8% vs. 8.8%, p=0.008, although this did not attain significance after adjustment to gestational age. No differences were noted in placental histology between the groups. GDM in IVF is associated with a significantly higher rate of adverse neonatal outcomes, as compared with non-assisted pregnancies complicated by GDM. Placental histology does not shed light on these clinical associations.

Comparison of perinatal outcomes and placental histology between IVF and unassisted pregnancies complicated by placenta-previa

Placenta previa (PP) is more prevalent in in-vitro-fertilization (IVF) pregnancies, but the mechanism is unclear. We aimed to compare the clinical characteristics and placental histology of pregnancies complicated by PP in IVF and unassisted pregnancies.

Association Between Ambient Air Pollutants Exposure and Preterm Birth in Women Who Underwent in vitro Fertilization: A Retrospective Cohort Study From Hangzhou, China.

Objectives: Exposure to air pollutants has been linked to preterm birth (PTB) after natural conception. However, few studies have explored the effects of air pollution on PTB in patients who underwent in vitro fertilization (IVF). We aimed to investigate the association between ambient air pollutants exposure and PTB risk in IVF patients.Methods: This retrospective cohort study included 2,195 infertile women who underwent IVF treatment from January 2017 and September 2020 in Hangzhou Women's Hospital. Totally 1,005 subjects who underwent a first fresh embryo(s) transfer cycle were analyzed in this study. Residential exposure to ambient six air pollutants (PM2.5, PM10, SO2, NO2, CO, O3) during various periods of the IVF timeline were estimated by satellite remote-sensing and ground measurement. Cox proportional hazards models for discrete time were used to explore the association between pollutants exposure and incident PTB, with adjustment for confounders. Stratified analyses were employed to explore the effect modifiers.Results: The clinical pregnancy and PTB rates were 61.2 and 9.3%, respectively. We found that PM2.5 exposure was significantly associated with an increased risk of PTB during 85 days before oocyte retrieval [period A, adjusted hazard ratio, HR=1.09, 95%CI: 1.02–1.21], gonadotropin start to oocyte retrieval [period B, 1.07 (1.01–1.19)], first trimester of pregnancy [period F, 1.06 (1.01–1.14)], and the entire IVF pregnancy [period I, 1.07 (1.01–1.14)], respectively. An interquartile range increment in PM10 during periods A and B was significantly associated with PTB at 1.15 (1.04–1.36), 1.12 (1.03–1.28), and 1.14 (1.01–1.32) for NO2 during period A. The stratified analysis showed that the associations were stronger for women aged <35 years and those who underwent two embryos transferred.Conclusions: Our study suggests ambient PM2.5, PM10, and NO2 exposure were significantly associated with elevated PTB risk in IVF patients, especially at early stages of IVF cycle and during pregnancy.

Uncomplicated oocyte donation pregnancies display an elevated CD163-positive type 2 macrophage load in the decidua, which is associated with fetal-maternal HLA mismatches.

ProblemThe embryo of an oocyte donation (OD) pregnancy is completely allogeneic to the mother, which may challenge the maternal immune system to tolerize the fetus. Decidual macrophages are essential in maintaining a healthy pregnancy, and type 2 macrophages may exhibit immune suppressive activity. We hypothesized that the composition of decidual macrophages is different between uncomplicated OD pregnancies and non‐OD in vitro fertilization (IVF) pregnancies, and is related to fetal‐maternal incompatibility.Method of studyWomen with uncomplicated pregnancy were enrolled: 25 singleton OD pregnancies and 17 non‐OD IVF pregnancies. The extent of immunohistochemical staining of CD14 (pan‐macrophage marker) and CD163 (type 2 macrophage marker) in both decidua basalis and parietalis was quantitated by digital image analysis. Maternal and fetal DNA was typed for human leukocyte antigen (HLA)‐A, ‐B, C, ‐DRB1, and ‐DQB1, and fetal‐maternal HLA mismatches were calculated.ResultsOD pregnancies showed a higher percentage of CD163+ staining (P = .040) and higher CD163/CD14 ratio (P = .032) in the parietalis than non‐OD IVF. The OD group was separated into a semi‐allogeneic group (≤5 fetal maternal HLA mismatches) and a fully allogeneic group (> 5 mismatches). The HLA‐fully‐allogeneic OD group, but not the HLA‐semi‐allogeneic OD group, showed significantly elevated CD163/CD14 ratio in the parietalis compared with the non‐OD IVF group (P < .05).ConclusionsUncomplicated OD pregnancies display a higher CD163‐positive cell fraction in the total decidual macrophage population compared to autologous pregnancies, which may suggest that a local type 2 macrophage‐related mechanism is needed to compensate for the higher fetal‐maternal HLA mismatch load.

Pregnancy outcomes after in vitro fertilization for moderate and severe endometriosis. A case-control study

IntroductionPrevious international studies showed that endometriosis could have a link with obstetrical complications, as an increased risk of preterm birth, gestational diabetes mellitus, and cesarean section. However, the results are difficult to interpret because biases are common, such as heterogeneity in the severity of the endometriosis cases included. That's why some complications as risk of miscarriage and post-partum hemorrhage are still debated. Our objective was to study pregnancy outcome after In Vitro Fertilization (IVF) in women suffering from rAFS stage III and IV endometriosis. MethodsWe conducted a case-control study between 2009 and 2019. We compared pregnancy outcomes after IVF in two groups of women matched by age, body mass index and smoking in two hospital centers. Group A was constituted by singleton pregnancies following ART for moderate and severe endometriosis (rAFS stage III and IV endometriosis). Group B was composed of singleton pregnancies in women with no endometriosis following ART for another reproductive disease. All women achieved pregnancy after 22 weeks. ResultsA total of 240 pregnant women were included: 80 singleton IVF pregnancies (group A) were compared with 160 singleton IVF pregnancies (group B). We observed an increased risk of placenta previa (12.5% Vs 1.9%; p = 0,001), and cesarean section (49.4% (n = 39) Vs 29.6% (n = 47) p = 0,004). Rate of postpartum hemorrhage was not significantly different in endometriosis group (11.2% Vs 7.5% p = 0.47). ConclusionDespite conflicting results in literature due to a lot of confounding variables, the impact of endometriosis on pregnancy is still debated in women suffering from rAFS III and IV endometriosis. In our study, we observed statistically higher rates of placenta previa and cesarean section but not an increased risk of postpartum hemorrhage. Further larger series are needed to confirm our findings and a possible link with other obstetrical complications. However, we think that an ART pregnancy in a context of severe endometriosis should be considered at risk of adverse obstetrical outcomes.

The impact of preimplantation genetic testing for aneuploidy on prenatal screening.

To determine whether preimplantation genetic testing for aneuploidy (PGT-A) is associated with a reduced risk of abnormal conventional prenatal screening results in singleton pregnancies conceived using in vitro fertilization (IVF). This was a retrospective cohort study of singleton IVF pregnancies conceived from a single tertiary care center between January 2014 and September 2019. Exclusion criteria included mosaic embryo transfers, vanishing twin pregnancies, and cycles with missing outcome data. Two cases of prenatally diagnosed aneuploidy that resulted in early voluntary terminations were also excluded. The primary outcome of abnormal first or second-trimester combined screening results was compared between two groups: pregnancy conceived after transfer of a euploid embryo by PGT-A vs. transfer of an untested embryo. Multivariable backwards-stepwise logistic regression with Firth method was used to adjust for potential confounders. Of the 419 pregnancies included, 208 (49.6%) were conceived after transfer of a euploid embryo by PGT-A, and 211 (50.4%) were conceived after transfer of an untested embryo. PGT-A was not associated with a lower likelihood of abnormal first-trimester (adjusted OR 1.64, 95% CI 0.82-3.39) or second-trimester screening results (adjusted OR 0.96, 95% CI 0.56-1.64). The incidences of cell-free DNA testing, fetal sonographic abnormalities, genetic counseling, and invasive prenatal diagnostic testing were similar between the two groups. Our data suggest that PGT-A is not associated with a change in the likelihood of abnormal prenatal screening results or utilization of invasive prenatal diagnostic testing. Counseling this patient population regarding the importance of prenatal screening and prenatal diagnostic testing, where appropriate, remains essential.

Different immunoregulatory components at the decidua basalis of oocyte donation pregnancies

Oocyte donation (OD) pregnancies are characterized by more fetal-maternal human leukocyte antigen (HLA) mismatches compared with naturally conceived (NC) and in vitro fertilization (IVF) pregnancies. The maternal immune system has to cope with greater immunogenetic dissimilarity, but involved immunoregulation remains poorly understood. We examined whether the amount of regulatory T cells (Tregs) and immunoregulatory cytokines in decidua basalis of OD pregnancies differs from NC and IVF pregnancies. The cohort included 25 OD, 11 IVF and 16 NC placentas, maternal peripheral blood, and umbilical cord blood of uncomplicated pregnancies. Placenta slides were stained for FOXP3, IL-10, IL-6, gal-1, TGF-β and Flt-1. Semi-quantitative (FOXP3+ Tregs) and computerized analysis (cytokines) were executed. The blood samples were typed for HLA class I and II to calculate fetal-maternal HLA mismatches. The percentage of Tregs was significantly higher in pregnancies with 4–6 HLA class I mismatches (n = 17), compared to 0–3 mismatches (n = 35; p = 0.04). Cytokine analysis showed significant differences between OD, IVF and NC pregnancies. Flt-1 was significantly lower in pregnancies with 4–6 HLA class I mismatches (p = 0.004), and in pregnancies with 6–10 HLA mismatches in total (p = 0.024). This study suggests that immunoregulation at the fetal-maternal interface in OD pregnancies with more fetal-maternal HLA mismatches is altered.

Maternal and neonatal outcomes following in vitro fertilization: A cohort study in Romania.

Although in recent years the number of pregnancies obtained through in vitro fertilization (IVF) has increased significantly, a higher incidence of complications has been identified in this group. The widespread development and use of IVF has led to an increasing rate of multiple pregnancies and thus their associated complications. However, whether these complications occur due to assisted reproduction or infertility problems remains to be elucidated. In the present study, a comparison was made of IVF pregnancies with spontaneous conception, and the risk of obstetric and neonatal complications was assessed. An ambispective observational cohort study was carried out between January 2017 and October 2021 at Elias University Emergency Hospital, Romania. The exposed cohort included 132 IVF pregnancies and the control cohort included 157 spontaneous pregnancies. The IVF group included 110 pregnancies with fresh embryo-transfer and 22 pregnancies with cryopreserved embryo-transfer. Obstetric, perinatal and neonatal complications were analysed by multivariable logistic analysis. The results showed that, IVF pregnancies had a higher risk of pregnancy-induced hypertension (OR=6.42, 95% CI=1.72-23.92) and placental abnormalities (OR=5.49, 95% CI=1.07-28.17). Neonates obtained through IVF had a higher risk of prematurity (OR=6.52, 95% CI=2.99-14.20), low birth weight (LBW) (OR=17.18, 95% CI=7.06-41.87), small for gestational age (OR=4.10, 95% CI=1.95-8.59) and were more frequently hospitalized in the Neonatal Intensive Care Unit (NICU) (OR=11.91, 95% CI=5.72-24.81). Nulliparous women were associated with an increased risk of NICU admission (OR=0.46, 95% CI=0.25-0.88) and risk of LBW (OR=0.37, 95% CI=0.19-0.75). Maternal age ≥35 years had no influence as a confounding variable. In conclusion, this cohort study showed that IVF pregnancies have a higher risk of obstetric and neonatal complications than pregnancies obtained by spontaneous conception.

PRETERM BIRTH AND LOW BIRTH WEIGHT IN SINGLETON PREGNANCIES AFTER IN VITRO FERTILIZATION- INFLUENCE OF INFERTILITY AND METHOD OF FERTILIZATION

The aim of our study was to determine the effect of infertility and the method of fertilization on the frequency of preterm birth and low birth weight in singleton pregnancies achieved by in vitro fertilization (IVF). The study was conducted in the period 01.2013 - 12.2017 and included 286 patients with births from singleton IVF pregnancies. Classical IVF received 107 patients (group A1) and ICSI fertilization - 148 (group A2). Cases with tubal infertility were 81 (group B1), and 85 were with male infertility (group B2). In group A1, birth prior to 37 weeks of gestation (w.g.) was found in 33 (30.8%) cases, compared to 26 (17.6%) in group A2 (p=0.029).In group A1, birth weight &lt;2500 g was observed in 27 (25.3%) of cases, and in group A2 - in 17 (11.5%) of cases (p=0.015). In group B1, birth prior to 37 w.g. was established in 26 (32.1%) of the cases, compared to 9 (10.6%) in group B2 (p=0.003). In group B1 there was birth weight &lt;2500 g in 19 (23.5%) of patients, compared to 6 (7.1%) in group B2 (p = 0.009). The average weight of the newborn and average duration of pregnancy was lower in groups with IVF fertilization and tubal infertility compared to ICSI fertilization and male infertility. Tubal infertility and classical IVF fertilization are independent risk factors that increase the frequency of preterm birth and low birth weight in IVF singleton pregnancies.

Endometrial Osseus Metaplasia during Infertility Evaluation: A Case Series

Aims: To highlight the pathogenesis of endometrial osseus metaplasia, its importance as a rare cause of infertility and the benefit of hysteroscopic evaluation of infertile women with risk factors for osseus metaplasia.&#x0D; Presentation of Case: A diagnosis of endometrial osseus metaplasia was confirmed histologically in three women undergoing diagnostic hysteroscopy as part of infertility evaluation. They all had chronic vaginal discharge and a preceding history of induced second trimester abortion. Two of the patients were referred for evaluation before in-vitro-fertilization (IVF). Hysteroscopy was done with a 30° telescope, initially using a 2-channel diagnostic sheath, which was later replaced with a 4-channel operating sheath for tissue retrieval.&#x0D; Discussion: Endometrial osseus metaplasia is a rare condition characterized by the presence of mature or immature bone in the endometrial cavity. Endometrial retention of embryonic tissue following an abortion is the commonest theory of etio-pathogenesis. It is an important cause of infertility and while other causes of infertility can be easily by-passed in an IVF cycle, endometrial factors may not be addressed by IVF alone, as a defective endometrium is a risk for failure. Although there is no consensus on routine hysteroscopy for women undergoing IVF, it is the mainstay of evaluation and treatment of women with endometrial osseus metaplasia.&#x0D; Conclusion: Only complete removal of metaplastic tissue would restore fertility, in patients with osseus metaplasia. Hysteroscopy done in infertile women with risk factors for endometrial osseus metaplasia may enhance early treatment and ultimately increase successful spontaneous and IVF pregnancy rates.

FIGO good practice recommendations on reduction of preterm birth in pregnancies conceived by assisted reproductive technologies.

FIGO (the International Federation of Gynecology and Obstetrics) supports assisted reproductive technologies (ART) to achieve pregnancy and supports their availability in all nations. However, the increased frequency of preterm birth must be taken into account. Therefore, before in vitro fertilization (IVF) is started, other approaches, including expectant management, should be considered. Single embryo transfer is the best approach to ensure a live, healthy child. However, increased risks for preterm birth are also associated with a singleton IVF pregnancy and should be discussed and contrasted with spontaneous conception. Increased preterm birth and other adverse pregnancy outcomes in singleton IVF cycles warrant investigations to elucidate and mitigate. Minimizing embryo manipulation during cell culture is recommended. Increased risk of preterm birth and other pregnancy complications in ART could reflect the underlying reasons for infertility. This information should be discussed and further explored.

Absolute Risk of Adverse Obstetric Outcomes Among Twin Pregnancies After In Vitro Fertilization by Maternal Age

Twin pregnancy is a common occurrence in pregnancies conceived with in vitro fertilization (IVF), but the absolute risk of adverse obstetric outcomes stratified by IVF, twin or singleton pregnancy, and maternal age are unknown. To estimate the absolute risk of adverse obstetric outcomes at each maternal age among twin pregnancies conceived with IVF. This retrospective cohort study included pregnant women with infants born from January 1, 2013, to December 31, 2018, based on the Hospital Quality Monitoring System in China. Data were analyzed from September 1, 2020, to June 30, 2021. Twin pregnancy with IVF (IVF-T), singleton pregnancy with IVF (IVF-S), twin pregnancy with non-IVF (nIVF-T), and singleton pregnancy with non-IVF (nIVF-S). Sixteen obstetric outcomes, including 10 maternal complications (gestational hypertension, eclampsia and preeclampsia, gestational diabetes, placenta previa, placental abruption, placenta accreta, preterm birth, dystocia, cesarean delivery, and postpartum hemorrhage) and 6 neonatal complications (fetal growth restriction, low birth weight, very low birth weight, macrosomia, malformation, and stillbirth). Among 16 879 728 pregnant women aged 20 to 49 years (mean [SD] age, 29.2 [4.7] years), the twin-pregnancy rates were 32.1% in the IVF group and 1.5% in the non-IVF group (relative risk, 20.8; 95% CI, 20.6-20.9). The most common adverse obstetric outcomes after pregnancy conceived with IVF were cesarean delivery (88.8%), low birth weight (43.8%), preterm birth (39.6%), gestational diabetes (20.5%), gestational hypertension and preeclampsia and eclampsia (17.5%), dystocia (16.8%), and postpartum hemorrhage (11.9%). The absolute risk of most adverse obstetric outcomes in each subgroup presented in 2 dominant patterns: Pattern A indicated the absolute risk ranging from IVF-T to nIVF-T to IVF-S to nIVF-S, and pattern B indicated the absolute risk ranging from IVF-T to IVF-S to nIVF-T to nIVF-S. Both patterns showed an elevated obstetric risk with increasing maternal age in each subgroup. In this cohort study, twin pregnancy, IVF, and advanced maternal age were independently associated with adverse obstetric outcomes. Given these findings, promotion of the elective single embryo transfer strategy is needed to reduce multiple pregnancies following IVF technologies. Unnecessary cesarean delivery shouldh be avoided in all pregnant women.

SPERM DNA FRAGMENTATION TEST IN ADDITION TO GENERAL SEMEN TEST MAY LEAD TO ELUCIDATION OF POTENTIAL FACTORS FOR PREDICTING IVF OUTCOMES

Female factors are very important in determining the success of in vitro fertilization (IVF). However, many reports have shown that male factors also affect the success or failure of IVF. Therefore, the sperm evaluation is important, semen examination criteria based on conventional methods alone is not a primary factor of consideration for determining IVF embryonic potential, pregnancy rates, and miscarriage rates after transplantation. We performed and analyzed the sperm DNA fragmentation index (DFI) and general semen test based on the WHO criteria and compared the two using semen factors. This study was conducted from June 2020 to December 2020. A total of 134 male patients with the main complaint of infertility who requested semen testing were included. We evaluate sperm motility using an automatic sperm analyzer based on the WHO criteria and sperm morphology via the Kruger test (general semen tests). DFI and general semen test were conducted in accordance with the WHO criteria, and correlations between the two tests were investigated. The WHO criteria were set as the cutoff value for each of the following factors: fluid volume, concentration, motility, and normal morphology, and compared with the DFI results. The mean age of the 134 patients at the time of the sperm tests was 38.8±6.0 years (range=26-52 years). The subjects had a mean DFI of 15.6±11.5% and the DFI increased with age (r=0.2319, p<0.01). In contrast, the concentration, motility, and normal morphology decreased as the DFI increased (concentration; r=-0.1992, p<0.05; motility; r=-0.2672, p<0.01; normal morphology; r=-0.2881, p<0.001). Patients who satisfied the WHO criteria in terms of sperm concentration, motility, and normal morphology had a significantly lower DFI than the group that did not satisfy the criteria (concentration p<0.05; motility p<0.01; normal morphology p<0.01). Therefore, evaluation with a general semen test based on the WHO criteria should be regarded as a qualitative evaluation of all factors other than fluid volume. Male infertility due to DFI should be suspected when in vitro fertilization results are poor despite normal semen findings based on the WHO criteria. The results of this study suggest that the DFI test may be an important evaluation in follow-up semen analyses.

PLACENTA PREVIA IN IVF AND UNASSISTED PREGNANCIES – PERINATAL OUTCOMES AND PLACENTAL HISTOLOGY

Placenta previa (PP) is more prevalent in in-vitro-fertilization (IVF) pregnancies, but the mechanism is unclear. We aimed to compare the clinical characteristics and placental histology of pregnancies complicated by (PP) in IVF and unassisted pregnancies.

P–743 The fertility paradox: the need for contraception after in vitro fertilisation

Abstract Study question What are a woman’s contraceptive needs after successful in vitro fertilisation (IVF) pregnancy? and how should services respond to help prevent unintended pregnancies? Summary answer Women who have IVF pregnancies require tailored, postnatal contraception counselling. Services must provide evidence-based information about the risks of spontaneous conception to engage them effectively. What is known already Women undergoing IVF are an increasingly heterogeneous group with a wide range of causative subfertility factors. Furthermore, increasingly, women are accessing treatment primarily for reasons other than subfertility. The evidence relating to rates of spontaneous conception post assisted conception varies widely according to population, cause of subfertility, type and outcome of fertility treatment and length of follow-up. A recent large retrospective UK cohort study estimated the treatment-independent live birth rate after IVF live birth over 5 year follow up as 15% [https://doi.org/10.1093/humrep/dez099]. We aim to explore the experiences and views about contraception among this diverse group of women. Study design, size, duration A qualitative study of the views of women who have had spontaneous pregnancies after successful IVF was conducted in September/October 2020. A qualitative approach of in-depth interviews was chosen to allow exploration of individual experiences in an area not much studied previously. The sample consisted of twenty interviewees from around the UK. Participants/materials, setting, methods Purposive and snowballing sampling methods were used with eligible participants recruited from a range of sources including social media and peer networks. The sample included a wide range of spontaneous pregnancy outcomes after successful IVF, including single and multiple livebirths, miscarriage, ectopic pregnancy and termination of pregnancy. The framework method was used for analysis using NVivo12 software. Main results and the role of chance Contraceptive choices were subject to a complex and dynamic interaction of influencing factors including i) beliefs regarding their own subfertility, ii) desire for more children and iii) their views on contraception. After IVF pregnancy, the majority of women (n = 15) used no contraception or ineffective methods (inconsistent condom use or withdrawal) before their next pregnancy with only two women using hormonal methods (progesterone-only pill). Spontaneous pregnancy was not universally welcomed in this group and the inter-pregnancy intervals were often short (n = 15, less than 18 months) or very short (n = 6, less than 12 months). After subsequent spontaneous pregnancy, use of contraception and the most effective (long-acting reversible) methods remained low. Women held persistent beliefs regarding their subfertility despite subsequent spontaneous pregnancy (or pregnancies). Women associated aspects of the IVF process (e.g. need for multiple cycles, low numbers of eggs collected etc.) with a sense of personal failure, despite an ultimately “successful” outcome resulting in livebirth. This may contribute to or reinforce their self-belief in subfertility. Other specific barriers to contraception use, in women having IVF, included lack of knowledge of the likelihood of spontaneous pregnancy, lack of contraceptive experience and inherent incentives towards shorter inter-pregnancy intervals. Limitations, reasons for caution There is potential recall bias with some women recalling experiences associated with IVF treatment more than ten years ago. However our sample included women who were currently pregnant as well as women who were further towards the end of their reproductive life to capture a range of experiences. Wider implications of the findings: The contraceptive needs of women having IVF pregnancies are being overlooked. Fertility services should take responsibility for providing accurate information on the risks of subsequent spontaneous pregnancy in this population. Maternity and community healthcare professionals must address women’s perceptions of their fertility in order to engage them in contraception counselling. Trial registration number N/A

P–395 Obstetric and perinatal outcomes of pregnancies resulting from fresh versus frozen embryo transfer – a sibling cohort

Abstract Study question We aimed to compare obstetric and perinatal outcomes between pregnancies conceived by in vitro fertilization (IVF) with fresh embryo transfer and frozen embryo transfer (FET) in the same women. Summary answer IVF pregnancies following fresh and FET entailed the same obstetric and perinatal outcomes, when compared in the same women. What is known already: There seems to be a difference in adverse outcomes between pregnancies following fresh and FET, as fresh transfer has repeatedly been associated with a higher risk of preterm birth and small for gestational age neonates, and the FET with preeclampsia and large for gestational age neonates. The overall lower incidence of adverse obstetric outcomes in FET may relate to the transfer of an embryo to a uterine environment in the setting of more physiological estradiol level but may also relate to patient characteristics which allow for freezing and subsequent transfer. Study design, size, duration This was a retrospective cohort of 214 deliveries during a 13-year period. Participants/materials, setting, methods The study was performed in a tertiary hospital. The cohort included live singleton deliveries (&amp;gt;24 weeks of gestation) and excluded pregnancies following egg donation. Each fresh transfer IVF pregnancy was matched to a FET pregnancy by the same woman (1:1 ratio). Main results and the role of chance A total of 107 fresh transfer pregnancies were matched to 107 FET pregnancies, in the same women. Mean maternal age was lower in the fresh transfer group compared to the FET group (30.4 vs. 32.5 years, p &amp;lt; 0.001), as was body mass index (BMI) (p = 0.001). A higher rate of nulliparity was noted in fresh transfer pregnancies (64.5% vs. 12.1%, p &amp;lt; 0.001). Mean birthweight was higher in the FET group (3160 vs. 3081 grams, respectively, p &amp;lt; 0.001), although the rates of low birth weight and small for gestational age neonates did not differ between the groups. Preterm deliveries occurred in 10.3% and 9.3% of fresh transfer and FET pregnancies respectively, p = 0.79. On multivariate linear regression analysis, the type of embryo transfer - FET or fresh - was not independently associated with birthweight, after adjustment for women’s age, nulliparity and BMI. Limitations, reasons for caution The study relied on coding in patient files, and thus certain data were missing for analysis, such as paternal identity. In addition, women included had at least two successful IVF pregnancies, and at least one cycle in which embryo freezing was performed. This may confer a selection bias. Wider implications of the findings: Our study of sibling deliveries after fresh and FET, points to a similar prognosis for the main obstetric and perinatal outcomes. This adds to current research which points to similar development of children following fresh and FET and is reassuring for clinicians consulting patients who are eligible for both options. Trial registration number Not applicable

O-216 Culture medium used in IVF-treatment impacts post-implantation embryonic growth and developmental trajectories in a sex-specific manner

Abstract Study question What is the (sex-specific) impact of two different culture media used in in vitro fertilization (IVF) treatment on post-implantation growth and development? Summary answer Embryos, especially males, cultured in SAGE 1-Step grow and morphologically develop faster in the first trimester, when compared to those cultured in Vitrolife G-1 PLUS. What is known already Increasing success rates after IVF can be attributed to several advancements, such as improved culture conditions. Culture media are of special interest, as they supply the embryo with essential nutrients and have previously been shown to impact birthweight. Moreover, IVF pregnancies are associated with an increased male:female ratio. However, it is unknown if culture media also have an impact prenatally. Therefore, our aim is to study the (sex-specific) impact of two different culture media (SAGE 1-Step and Vitrolife G-1 PLUS) used in IVF treatment on first-trimester embryonic growth and development, and fetal outcomes. Study design, size, duration Women with a viable singleton pregnancy were included before 10 weeks of gestation in the Rotterdam Periconception Cohort, an ongoing prospective tertiary hospital-based study, conducted since November 2009. Participants/materials, setting, methods A total of 879 pregnancies were included; 153 after culture in Vitrolife G-1 PLUS, 251 after culture in SAGE 1-Step and 475 naturally conceived. First-trimester growth and development, defined by serial crown-rump length (CRL), embryonic volume (EV) and Carnegie stages measurements were performed using state-of-the-art imaging techniques. Secondary outcomes included second trimester estimated fetal weight (EFW) and birth outcomes, and were retrieved from medical records. Main results and the role of chance Linear mixed model analyses, adjusted for gestational age and maternal characteristics, showed that embryos cultured in SAGE 1-Step grow faster than those cultured in Vitrolife G-1 PLUS (βEV 0.030 ∛cm3 (95%CI 0.008-0.052), p=0.007). CRL and Carnegie stages were not statistically different between culture media. After stratification for fetal sex, similar results were observed for male embryos (βEV 0.048 ∛cm3 (95%CI 0.015-0.081), p=0.005), but not for female embryos. EFW and birth outcomes were comparable between culture media in the total population and after stratification for fetal sex. Embryos cultured in SAGE 1-Step also grow faster than those conceived naturally (βEV 0.033 ∛cm3 (95%CI 0.006-0.060), p=0.018). This association was also most pronounced in male embryos (βEV 0.066 ∛cm3 (95%CI 0.024-0.108), p=0.002). Limitations, reasons for caution Although this study has a prospective design, its observational character does not exclude residual confounding. Furthermore, the external validity of this explorative study is limited, since participants were recruited from a tertiary university hospital. Wider implications of the findings Culture in SAGE 1-Step culture medium is associated with faster first-trimester growth and development, especially in male embryos. This may be the result of altered susceptibility to preimplantation environmental stressors. Further research should focus on the (sex-specific) impact of culture media on postnatal development and the susceptibility to non-communicable diseases. Trial registration number N/A

P–380 Differential concentrations of maternal and fetal hemopexin and α1-microglobulin in preeclampsia from IVF pregnancies depending on the presence of corpus luteum at embryo transfer

Abstract Study question Does the presence of corpus luteum (CL) in in vitro fertilization (IVF) treatments affect maternal and fetal concentrations of hemopexin and α1-microglobulin in preeclampsia? Summary answer Decreased hemopexin and increased α1-microglobulin levels in maternal and fetal blood in IVF pregnancies with absence of CL particularly in pregnancies complicated by preeclampsia. What is known already: Pregnancies after frozen embryo transfer (FET) in programmed cycles have higher rates of hypertensive disorders of pregnancy, suggesting a link between the absence of CL in programmed cycles and adverse maternal outcomes.Cardiovascular function is impaired early in pregnancy in women conceiving by IVF treatments in the absence of CL.Plasma relaxin–2, a potent vasodilator and stimulus of decidualization, has been reported to be undetectable in a non-CL cohort, but markedly elevated in a multiple-CL cohort through pregnancy.Hemopexin and α1-microglobulin act as scavengers that eliminate free heme-groups responsible for hemoglobin-induced oxidative stress known to contribute to preeclampsia development. Study design, size, duration A case-control study of 160 singleton pregnancies recruited from 2016 to 2020, including 54 spontaneous pregnancies from fertile couples, 50 conceived by IVF following fresh embryo transfer (ET) and FET in natural cycle (presence of CL) and 56 IVF after fresh oocyte-donation or FET in programmed cycles (absence of CL). Pregnancies were subclassified according to the presence of preeclampsia in uncomplicated, preeclampsia and severe preeclampsia cases. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. Spontaneous pregnancies from fertile couples were randomly selected from our general population and matched to IVF by gestational age at birth. Hemopexin and α1-microglobulin concentrations were measured by ELISA in maternal and cord plasma collected at delivery. All comparisons were adjusted for age, ethnicity, prematurity, birthweight centile, oocyte-donation and FET cycles. Main results and the role of chance Parental ethnicity, body mass index, exposure to aspirin and corticoids during pregnancy, mean gestational age at birth and birthweight were similar in all study groups. While maternal hemopexin levels were lower in treatments without CL, the IVF group with one or several CL showed significantly increased hemopexin concentrations, both in uncomplicated and preeclampsia cases (uncomplicated: spontaneous conceptions median 1520 ug/ml [interquartile range 1054–1746], IVF with CL 1554 [1315–1778], IVF without CL 1401 [1130–1750]; Preeclampsia: spontaneous conceptions 1362 [1121–1667], IVF with CL 1372 [403–2558], IVF without CL 1215 [971–1498]). Maternal α1-microglobulin was significantly higher in the absence of CL in severe preeclamptic cases as compared to spontaneous pregnancies and IVF with CL (spontaneous conceptions median 23 ug/ml [interquantile range 20–24], IVF with CL 24 [24–26], IVF without CL 26 [25–28]). The cord blood profiles were identical to the maternal for both biomarkers. Overall, and in line with previous studies, preeclamptic pregnancies independently of the mode of conception, showed decreased concentrations of hemopexin and increased concentrations of α1-microglobulin both in maternal and fetal plasma, with more pronounced changes in severe preeclampsia cases. Limitations, reasons for caution Infertility factors contribution to the outcome cannot be unraveled from the assisted reproductive technologies procedure itself as we have only included spontaneous pregnancies from fertile couples. Adjustments for oocyte-donation and FET modalities were performed due to the higher proportion of these features in the ET in programmed cycles group. Wider implications of the findings: These findings acknowledge physiological differences between pregnancies following ET in stimulated and natural versus programmed cycles, supporting the hypothesis that the CL activity could influence perinatal results. This approach to perinatal outcomes in IVF patients could lead to changes in ET protocols in order to develop a CL if possible. Trial registration number Not applicable