Pregnancy Birth Research Articles

Effect of prematurely elevated late follicular progesterone on pregnancy outcomes following ovarian stimulation-intrauterine insemination for unexplained infertility: secondary analysis of the AMIGOS trial.

What is the relationship between late follicular phase progesterone levels and clinic pregnancy and live birth rates in couples with unexplained infertility undergoing ovarian stimulation with IUI (OS-IUI)? Late follicular progesterone levels between 1.0 and <1.5 ng/ml were associated with higher live birth and clinical pregnancy rates while the outcomes in groups with higher progesterone levels did not differ appreciably from the <1.0 ng/ml reference group. Elevated late follicular progesterone levels have been associated with lower live birth rates after fresh embryo transfer following controlled ovarian stimulation and egg retrieval, but less is known about whether an association exists with outcomes in OS-IUI cycles. Existing studies are few and have been limited to ovarian stimulation with gonadotrophins, but the use of oral agents, such as clomiphene citrate and letrozole, is common with these treatments and has not been well studied. The study was a prospective cohort analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Frozen serum was available for evaluation from 2121 cycles in 828 AMIGOS participants. The primary pregnancy outcome was live birth per cycle, and the secondary pregnancy outcome was clinical pregnancy rate per cycle. Couples with unexplained infertility in the AMIGOS trial, for whom female serum from day of trigger with hCG was available in at least one cycle of treatment, were included. Stored frozen serum samples from day of hCG trigger during treatment with OS-IUI were evaluated for serum progesterone level. Progesterone level <1.0 ng/ml was the reference group for comparison with progesterone categorized in increments of 0.5 ng/ml up to ≥3.0 ng/ml. Unadjusted and adjusted risk ratios (RR) and 95% CI were estimated using cluster-weighted generalized estimating equations to estimate modified Poisson regression models with robust standard errors. Compared to the reference group with 110/1363 live births (8.07%), live birth rates were significantly increased in cycles with progesterone 1.0 to <1.5 ng/ml (49/401 live births, 12.22%) in both the unadjusted (RR 1.56, 95% CI 1.14, 2.13) and treatment-adjusted models (RR 1.51, 95% CI 1.10, 2.06). Clinical pregnancy rates were also higher in this group (55/401 clinical pregnancies, 13.72%) compared to reference group with 130/1363 (9.54%) (unadjusted RR 1.46, 95% CI 1.10, 1.94 and adjusted RR 1.42, 95% CI 1.07, 1.89). In cycles with progesterone 1.5 ng/ml and above, there was no evidence of a difference in clinical pregnancy or live birth rates relative to the reference group. This pattern remained when stratified by ovarian stimulation treatment group but was only statistically significant in letrozole cycles. The AMIGOS trial was not designed to answer this clinical question, and with small numbers in some progesterone categories our analyses were underpowered to detect differences between some groups. Inclusion of cycles with progesterone values above 3.0 ng/ml may have included those wherein ovulation had already occurred at the time the IUI was performed. These cycles would be expected to experience a lower success rate but pregnancy may have occurred with intercourse in the same cycle. Compared to previous literature focusing primarily on OS-IUI cycles using gonadotrophins, these data include patients using oral agents and therefore may be generalizable to the wider population of infertility patients undergoing IUI treatments. Because live births were significantly higher when progesterone ranged from 1.0 to <1.5 ng/ml, further study is needed to clarify whether this progesterone range may truly represent a prognostic indicator in OS-IUI cycles. Oklahoma Shared Clinical and Translational Resources (U54GM104938) National Institute of General Medical Sciences (NIGMS). AMIGOS was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, and U10HD055925. Research made possible by the funding by American Recovery and Reinvestment Act. Dr Burks has disclosed that she is a member of the Board of Directors of the Pacific Coast Reproductive Society. Dr Hansen has disclosed that he is the recipient of NIH grants unrelated to the present work, and contracts with Ferring International Pharmascience Center US and with May Health unrelated to the present work, as well as consulting fees with May Health also unrelated to the present work. Dr Diamond has disclosed that he is a stockholder and a member of the Board of Directors of Advanced Reproductive Care, Inc., and that he has a patent pending for the administration of progesterone to trigger ovulation. Dr Anderson, Dr Gavrizi, and Dr Peck do not have conflicts of interest to disclose. N/A.

Association of Previous Surgical Miscarriage with Risk of Preterm Subsequent Pregnancy in Females Presenting in a Tertiary Care Hospital

Surgical miscarriages are a common obstetric issue with potential long-term effects on subsequent pregnancies. Objective: To evaluate the association between previous surgical miscarriages and the risk of preterm birth in later pregnancies. Methods: This descriptive cross-sectional study was conducted at the Department of Obstetrics &amp; Gynaecology, Mekran Medical College (MMC), Turbat, from November 2023 to April 2024. Data collected included age at second pregnancy, BMI, socioeconomic status, smoking status, and medical conditions such as hypertension and diabetes. Collected data were processed and analyzed using IBM SPSS, version 27.0. Results: The study included 230 patients with a history of miscarriage. Participants with ≥ 3 previous miscarriages had significantly higher odds of all-cause preterm birth (OR = 8.19, p = 0.050), spontaneous preterm birth (OR = 6.38, p = 0.005), and induced preterm birth (OR = 4.64, p &lt; 0.001) compared to those with 1 previous miscarriage. After adjustment, those with ≥ 3 previous miscarriages had higher odds of all-cause (OR = 4.92, p &lt; 0.001) and spontaneous preterm birth (OR = 5.79, p = 0.005), but not induced preterm birth (OR = 5.63, p = 0.050). Conclusions: Our study results revealed a significant association between a history of previous surgical miscarriages and the probability of preterm births in subsequent pregnancies. These findings underscore the need for clinical monitoring and interventions for women with a history of surgical miscarriages

Retraction Note: Progesterone effects on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial.

Retraction Note: Progesterone effects on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial.

Assisted Reproductive Technology During COVID-19: A Population-Based Study Of Pregnancy Outcomes.

We assessed the impact of the COVID-19 pandemic on the pregnancy outcomes of patients who used assisted reproductive technology. We conducted a population-based cohort study of 443,101 patients who conceived naturally or with assisted reproductive technology between December 2015 and July 2021 and had a delivery in hospitals of Quebec, Canada. The main exposure measure was use of assisted reproductive technology before or during the pandemic. Outcomes included preeclampsia, preterm birth, and other pregnancy complications. We used adjusted log-binomial regression models to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association of assisted reproductive technology with adverse pregnancy outcomes compared with natural conception before vs. during the pandemic. In secondary analyses, we examined the association of COVID-19 infection with pregnancy outcomes among women who used assisted reproductive technology. Compared with natural conception, assisted reproductive technology was associated with an increased risk of preeclampsia (RR 1.43; 95% CI 1.21-1.68), preterm birth (RR 2.07; 95% CI 1.84-2.33), and low birth weight (RR 1.94; 95% CI 1.72-2.20) during the pandemic. However, the same risks were also present before the pandemic. Compared with no infection, COVID-19 infection was not associated with adverse outcomes among women who conceived with assisted reproductive technology. This study suggests that the COVID-19 pandemic did not significantly impact the pregnancy outcomes of women who underwent assisted reproductive procedures in Quebec. The findings are reassuring for patients concerned about the potential reproductive effects of the pandemic.

Long-Term Maternal and Neonatal Outcomes Following Birth in Fetal Growth Restricted Pregnancies

Long-Term Maternal and Neonatal Outcomes Following Birth in Fetal Growth Restricted Pregnancies

P-767 Preterm birth in singleton pregnancies conceived by in-vitro fertilization or intracytoplasmic sperm injection: a systematic review with umbrella meta-analysis

Abstract Study question What is the risk level and potential etiology of preterm birth (PTB) in singleton pregnancies from in-vitro fertilization (IVF) or intra-cytoplasmic injection (ICSI)? Summary answer Singleton pregnancies from IVF/ICSI have, on average, double the risk of PTB compared to natural conceptions, with a higher risk for iatrogenic than spontaneous PTB. What is known already IVF/ICSI pregnancies are associated with a higher PTB risk, with a predominant effect mediated by the effect of multiples and a poor understanding of underlying etiology, particularly in singletons. According to the European IVF Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE), about 16% of singleton conceived through IVF/ICSI were born preterm in 2019. Considering the global a shift towards single embryo transfers (ETs), it becomes crucial to precisely determine and convey the PTB risk specific to singleton pregnancies conceived through IVF/ICSI, collecting all available evidence on supposed PTB etiology. Study design, size, duration A comprehensive search in major online databases was conducted up to December 31, 2023. Eligible studies were systematic reviews with quantitative data. The primary aim was to quantify PTB risk in singletons conceived by IVF/ICSI compared to natural pregnancies. Secondary objectives included assessing very preterm birth (VPTB) risk and exploring PTB’s etiology, phenotype, and initiation. PTB and VPTB were defined by the World Health Organization as delivery before 37 or 32 weeks, respectively. Participants/materials, setting, methods Random-effects meta-analysis models were used for pooling effect measures. Estimates were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Information available on etiology, phenotype, initiation of PTB and relevant moderators was extracted and employed for subgroup analyses. The extent of overlap in the original studies was measured using the Corrected Covered Area (CCA) assessment. The quality of the included reviews was evaluated with the AMSTAR 2 tool and quality of evidence by GRADE. Main results and the role of chance Twelve meta-analyses with a total of 16,522,917 pregnancies were included. IVF/ICSI singletons showed a significantly higher risk of PTB compared to natural conception (PTB ˂37 weeks: OR: 1.72, 95% CI: 1.57-1.89). The pooled risk estimate was higher for births below 32 weeks (VPTB &amp;lt;32 weeks: OR: 2.19, 95%CI: 1.82-2.64). Influential analysis reinforced the strength of this association. Subgroup analyses investigating supposed etiology revealed a comparable risk magnitude for spontaneous PTB (OR 1.79, 95% CI:1.56-2.04) and a greater risk for iatrogenic PTB (OR: 2.28, 95%CI: 1.72–3.02). PTB risk was consistent in the subgroup of conventional IVF (OR: 1.95, 95% CI: 1.76-2.15) and higher in the subgroup of fresh-only ETs (OR: 1.79, 95% CI: 1.55-2.07) compared to frozen-thawed ETs (OR: 1.39, 95%CI: 1.34-1.43). CCA assessment showed minimal study overlap (13%). The quality of the evidence by GRADE assessment was judged as low to very low. Limitations, reasons for caution The methodological quality of the included reviews, as rated by AMSTAR 2, was judged as low to very low. Most included studies lacked granular data on IVF/ICSI indications and on specific PTB etiology, phenotypes, or initiation. Wider implications of the findings The risk of PTB is about double in IVF/ICSI singleton pregnancies compared to naturally conceived, with paucity of available data on PTB aetiology, phenotype, or initiation. The greater risk increase involves iatrogenic PTB from fresh ET and VPTB, likely due to placental aetiology. Trial registration number PROSPERO ID: CRD42023411418

O-092 Prevalence of multiple gestation births and perinatal outcomes in pregnancies secondary to clomiphene citrate treatment: a nationwide cohort study

Abstract Study question Is the incidence of multiple gestation births higher in pregnancies obtained after clomiphene citrate (CC) treatment compared to spontaneous pregnancies? Summary answer The rate of multiple gestation births in pregnancies obtained after CC treatment is significantly increased compared to spontaneous pregnancies. What is known already CC is a selective estrogen modulator frequently used to induce ovulation in infertile women. Data regarding the prevalence of multiple gestation births and adverse perinatal outcomes after CC are contradicting and based on meta-analysis of small sample size studies. Multiple gestations are frequently associated with complications such as preeclampsia, premature labor, and growth restriction, which contribute to higher mortality and morbidity rates. Study design, size, duration Using the French National Health Data System (SNDS) spanning 2013 to 2019, we conducted a nationwide cohort study including all pregnancies lasting more than 22 weeks of gestation, in women aged between 18-43 years. Participants/materials, setting, methods For each women, the first pregnancy during study was included. Women with the dispensing of IVF/ICSI treatment and/or gonadotrophins were excluded. Pregnancies exposed to CC (during the period [-60days,-11days] before the beginning of the pregnancy) were 1:10 matched to unexposed pregnancies. Pregnancies exposed to CC between 12 to 2months or less than 11 days before the beginning of the pregnancy were excluded to mitigate misclassification bias. The primary outcome was the multiple gestation birth rate. Main results and the role of chance Of 3,173,013 pregnancies, 32,010 (10 ‰) occurred in women exposed to clomiphene. The multiple pregnancy rate was significantly higher in pregnant women exposed with CC compared to matched controls (odd ratio 4.1, 95% CI [3.9-4.3]) such as twin pregnancies (OR 4.1, 95% CI [3.9-4.3]) and triple or more pregnancies (OR 5.1, 95% CI [3.8-7.2]). Women exposed to CC presented significantly more adverse obstetrical and perinatal outcomes, including stillbirths, premature delivery threats, premature rupture of membranes, gestational diabetes, placenta previa, gravid hypertension, pre-eclampsia, preterm birth, small for gestational age (SGA), C-section rate, and major birth defect rate. After stratification on multiple pregnancy and adjustment on confounders (history of psychiatric disease, diabetes, arterial hypertension, obesity and embryo reduction during pregnancy), women exposed to CC had a significantly higher risk of stillbirth, gestational diabetes, placenta previa, pre-eclampsia, preterm delivery and SGA in case of singleton pregnancies. Additionally, in the case of multiple pregnancies, they had a higher risk of placenta previa, preterm delivery, and SGA compared to non-exposed women. Limitations, reasons for caution The use of filled prescriptions as a measure of drug exposure could be subject to bias such as misclassification bias, although we attempt to mitigate it. Wider implications of the findings Clomiphene use is strongly associated with multiple gestation births and with adverse obstetrical and perinatal outcomes even in singleton pregnancies. These findings should provide awareness of practitioners and patients about its use. It underscore the importance of attentively monitoring follicular growth during the treatment process to avoid multiple pregnancies. Trial registration number NA

P-745 effectiveness and safety of consecutive single embryo transfer compared to double embryo transfer: results from UK HFEA registry

Abstract Study question How does two-consecutive single embryo transfer (2xSET) affect reproductive outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) compared to double embryo transfer (DET)? Summary answer 2xSET may provide greater or comparable live birth rates with lower multiple birth, preterm birth, and pregnancy loss or neonatal death rates compared to DET. What is known already Elective single embryo transfer (SET) in IVF/ICSI is widely encouraged over DET to minimise the risk of multiple birth and associated morbidities. Despite this, UK multiple birth rates following IVF remain higher than spontaneous conception, with 5% of IVF pregnancies resulting in multiple birth compared to 0.4%-1.2% multiple gestation rates following spontaneous conception. Owing to advancements in cryopreservation techniques, live birth and ongoing pregnancy rates are now comparable between fresh and frozen embryo transfer. Consequently, 2xSET has been suggested as an alternate technique to achieve comparable live birth rates with fewer multiple gestation pregnancies compared to DET. Study design, size, duration This retrospective cohort study was conducted using Human Fertilisation and Embryology Authority (HFEA) register data, which encompasses national data from all IVF clinics in the UK. Within this analysis, all women who underwent their first oocyte collection and IVF or ICSI treatment cycle with subsequent SET, DET or 2xSET between 2010 and 2019 using either blastocyst or cleavage stage embryos were included (N = 125,149). Participants/materials, setting, methods This national retrospective cohort study utilised UK HFEA register data from 2010-2019, including all women who underwent their first oocyte collection and subsequent embryo transfer (N = 125,149). The rate of live birth, multiple birth, preterm birth, and pregnancy loss or neonatal death was compared between SET, DET, and 2xSET IVF/ICSI pregnancies using either blastocyst or cleavage stage embryos, and was stratified by maternal age. Data analysis was conducted in RStudio v4.2, alpha equals 0.05. Main results and the role of chance 2xSET pregnancies following blastocyst-stage transfer achieved a greater live birth occurrence rate of 0.47 (0.13) (median (interquartile range)) than SET, 0.41 (0.13), and DET, 0.38 (0.13) (P &amp;lt; 0.05). When using SET as a reference standard, 2xSET achieved a lower multiple birth rate, odds ratio (OR) of 6.87 (95%CI 6.14-7.68), than DET, OR 28.20 (95%CI 25.20-31.57), and lower preterm birth rate; OR 1.11 (95%CI 1.06-1.15) in 2xSET, and OR 2.80 (95%CI 2.67-2.94) in DET. Pregnancy loss or neonatal death rate was also lower in 2xSET, OR 1.14 (95%CI 1.08-1.21), compared to DET, OR 2.11 (95%CI 1.98-2.24). Conversely, in cleavage-stage embryo transfer pregnancies, no significant difference in live birth occurrence rate was observed, achieving rates of 0.27 (0.21) for SET, 0.26 (0.13) for DET, and 0.29 (0.18) for 2xSET. 2xSET was less likely to result in multiple birth than DET, OR 0.14 (95%CI 0.11-0.19). Moreover, when using SET as a reference standard, 2xSET was less likely to result in preterm birth than DET, OR 1.02 (95%CI 0.87-1.23) and 2.48 (95%CI 2.17-2.82) respectively, as well as pregnancy loss or neonatal death, OR 1.07 (95%CI 0.85-1.35) and 2.03 (95%CI 1.70-2.42) respectively. Limitations, reasons for caution Certain confounders are not recorded within HFEA registry data, including patient body mass index (BMI), evaluation of embryo quality, and endometrial thickness at embryo transfer. Consequently, while our analysis identifies broad trends in embryo transfer success and morbidity, results may differ within certain patient populations. Wider implications of the findings 2xSET may provide greater or comparable live birth rates with lower multiple birth and morbidity than DET. Promotion of 2xSET where appropriate for maternal age and embryo quality should be implemented to enhance reproductive outcomes and reduce the risk of morbidity in IVF/ICSI pregnancies. Trial registration number Not Applicable

O-128 Can embryo re-expansion pattern post-biopsy for PGT-A have a predictive value on the outcome?

Abstract Study question Does re-expansion grade at 1 hour post-biopsy correlate with post-thawing re-expansion rate and live birth rate? Summary answer Embryo re-expansion 1-hour post-biopsy is associated with post-warming re-expansion and increased live birth. What is known already Blastocyst cryopreservation is a key component of PGT-A procedures. In non-PGT-A cycles, collapsing blastocysts before vitrification is commonly recommended to improve blastocyst viability. However, the procedure becomes more complex in PGT-A cycles.The European Society of Human Reproduction and Embryology (ESHRE) recommends an immediate freeze post-biopsy, although a definitive timeframe remains elusive. To date, no conclusive timing has been agreed upon. Some studies support prolonged culture post-biopsy (&amp;gt; 3hrs), citing improved implantation and pregnancy rates. Conversely, others advocate for rapid cryopreservation, endorsing an immediate approach within an hour, while mostly blastocysts are still collapsed due to the biopsy procedure. Study design, size, duration Retrospective study of 1141 single euploid blastocyst transfers (seFET) conducted between April 2021 and February 2023. Analysed factors included patients' age, BMI, embryo quality at biopsy and 1-hour post-biopsy (at vitrification), and the biopsy day. Live birth and Ongoing pregnancy (OPR), defined as viable pregnancy beyond 24 weeks, were assessed. Blastocysts were scored at a standardized time (1hr post TE-biopsy): 0 for complete collapse, 1 for starting re-expansion, and 2 for clear re-expanded cavity. Participants/materials, setting, methods PGT-A patients undergoing a seFET. Only cycles with embryos being biopsied on Days 5,6 or 7 and with a known pregnancy outcome were included. Main results and the role of chance Out of 1141 transfers, 461 transfers resulted in live birth (40.4%) and 108 were still ongoing above 24 weeks’ gestation at the time of last contact (9.4%) for a total OPR/LB rate of of 49.8%. One-hour post-biopsy 64.0% of blastocysts re-expanded to Grade 2, 29.3% to Grade 1, and 6.7% showed no re-expansion (Grade 0). The OPR was significantly different between embryos that re-expanded to grade 2, 1 or 0 (54.2%, 44.3% and 32.5%, respectively, P &amp;lt; 0.001). Regression analysis showed re-expanding to Grade 2 at 1-hour post-biopsy was significantly and independently associated with OPR/LB compared to embryos that did not re-expand (i.e., Grade 0) (aOR: 1.77, 95% CI: 1.01–3.12, P = 0.047), after adjusting for embryo quality metrics (ICM, TE grade, day of biopsy), body-mass index and endometrial preparation type. . Embryos with greater re-expansion 1-hour post-biopsy had higher re-expansion slopes post-thawing, indicating faster and greater re-expansion to the point of transfer. Results were significant for all trophectoderm categories (Grade A, B, and C; P = 0.016, &amp;lt;0.001 and &amp;lt;0.001, respectively). Moreover, re-expansion rate 1-hour post-biopsy was significantly and independently associated with post-thawing re-expansion slope after adjusting for ICM, TE, expansion grade and biopsy day (P &amp;lt; 0.001). Limitations, reasons for caution The re-expansion grading remains an in-house system that involves subjective assessment with a possible inter-observer variation. Wider implications of the findings This study clearly demonstrates that post-biopsy re-expansion pattern, obtained in a standardized approach, can be helpful for predicting live birth. It is a novel independent marker that is not reflected by ICM, TE quality or day of biopsy for selecting embryos for thawing and transfer. Trial registration number not applicable

P-022 Klinefelter syndrome couples are expected higher live birth rates than unexplained NOA couples after ICSI with testicular spermatozoa

Abstract Study question What are sperm retrieval rates (SRR) by microdissection TESE (micro TESE), fertilization rates, and pre- and post- implantation development in Klinefelter syndrome (KS) couples? Summary answer In KS couples, SRR, clinical pregnancy rates (CPR) per embryo transfer (ET), and live birth rates (LBR) per patient were higher than unexplained NOA couples. What is known already Micro TESE, in combination with ICSI, is presently used to treat infertility in cases of NOA including KS, which is the most common sex-chromosome disorder among infertile males, with a prevalence of 1 in 660 men and is a frequent cause of hypogonadism and infertility. There were few reports regarding ICSI outcomes in the couples of KS. The aim of this study is to assess the prevalence and the significance including SRR by micro TESE of ICSI outcomes with embryonic development in KS couples. Study design, size, duration A retrospective study was conducted in 212 patients with non-mosaic KS and 963 unexplained NOA patients with 46, XY without past history (unexplained NOA; not including after orchidopexy, KS, cryptozoospermia, post chemotherapy, mumps orchitis, etc) who underwent micro TESE and ICSI with fresh or cryopreserved testicular spermatozoa for their wives between September 2013 to November 2023. Participants/materials, setting, methods A total of 2204 azoospermic patients were examined for chromosomal analysis. We evaluated SRR of microdissection TESE, two pronuclei (2PN) rates, blastocyst development rates, good-quality blastocyst (Grade 3BB and above on day 5 by the Gardner scoring) rates, CPR per ET, and LBR per couple patient who underwent micro TESE. We did not undergo preoperative hormonal therapy for KS patients. Statistical analysis was performed using unpaired t-tests and chi-squared tests. Main results and the role of chance We identified 212 KS out of 2204 azoospermic patients (9.6%). SRR of the first attempt micro TESE in KS (91/175=52.0%) was significantly higher than unexplained NOA (166/768=21.6%) (p &amp;lt; 0.001). 2PN, blastocysts development, and good-quality blastocysts rates were 49.2%, 42.9%, 16.9% in KS and 50.8, 45.8%, 21.0% in unexplained NOA respectively. Only good-quality blastocysts rate of KS was significantly lower than that of unexplained NOA (p &amp;lt; 0.01). Taking into account deflection of wives age, each result was calculated at their age 38 or under, but they were the same. CPR and LBR per ET in KS (42.6%, 30.4%) were significantly higher than unexplained NOA (33.1%, 23.7%) (p &amp;lt; 0.01, p &amp;lt; 0.05). The couples were 26.4% (56/212) in KS and 12.0% (116/963) in unexplained NOA (p &amp;lt; 0.001) who have given birth or ongoing pregnancy up to now after underwent micro TESE. That is, KS couples were significantly easier to give birth than unexplained NOA. Rates of congenital disorders had no significant difference between KS and unexplained NOA. Limitations, reasons for caution We did not show the data using ejaculated sperm with KS. The natal outcomes and development of these children has not been fully investigated, long-term follow-up of babies of the KS couples is needed. Wider implications of the findings Micro TESE is particularly helpful for KS cases, but embryonic development depend on the quality of spermatozoa. However, if a blastocyst can be obtained, the expectation of having a child is considered to be high. These results were shown to be useful in informing azoospermic couples undergoing micro TESE. Trial registration number not applicable

P-162 Embryo transfer impact: a comprehensive national cohort analysis comparing maternal outcomes across varied embryo stages in fresh and frozen transfers

Abstract Study question What is the ideal choice between fresh and frozen embryos transfer, and should the transfer be done at the cleavage or blastocyst stage? Summary answer This study highlights the clinical pregnancy and live birth superiority of frozen embryo transfer in blastocysts but not in cleavage stage embryos. What is known already Frozen embryo transfer not only improves reproductive outcomes by increasing the chances of live birth and clinical pregnancy but also enhances safety by reducing the risks of OHSS and multiple pregnancies. Due to the consistent findings, there has been a growing discussion in recent years about whether it is advisable to adopt elective frozen embryo transfer as the standard practice. Study design, size, duration In this retrospective cohort study conducted in Taiwan, a comprehensive dataset from the national assisted reproductive technology (ART) database was utilized, covering the period from January 1st, 2013, to December 31st, 2017. The final cohort study encompassed eligible 51762 female participants who had undergone ART and embryo transfer. Pregnancy outcomes and maternal complications during the follow-up were assessed using the population registry dataset from January 1st, 2013, to December 31st, 2018. Participants/materials, setting, methods The study categorizes cases into groups based on whether they underwent fresh or frozen embryo transfers, with additional subgroups based on cleavage stage and blastocyst stage transfers. Exposure variables include clinical pregnancy rate, live birth rate, ovarian hyperstimulation syndrome (OHSS), pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, and preterm premature rupture of membranes (PPROM). Main results and the role of chance For pregnancy outcomes, frozen blastocyst transfers exhibited higher rates of clinical pregnancy (OR 1.33, 95%CI 1.25-1.42) and live births (OR 1.27, 95%CI 1.19-1.36) when compared to fresh blastocyst transfers. However, frozen cleavage stage transfers had lower rates of clinical pregnancy (OR 0.73, 95%CI 0.69-0.77) and live births (OR 0.79, 95%CI 0.74-0.84) compared to fresh cleavage stage transfers. For maternal complications, frozen embryo transfers were associated with reduced risks of OHSS (OR 0.02, 95%CI 0.02-0.03 for blastocyst and OR 0.05, 95%CI 0.03-0.09 for cleavage stage) compared to fresh embryo transfers, but were linked to a higher risk of pregnancy-induced hypertension (OR 1.43, 95%CI 1.19-1.73 for blastocyst and OR 1.23, 95%CI 1.29-1.82 for cleavage stage). No significant differences were observed in the incidence of gestational DM and PPROM among the various transfer groups. Limitations, reasons for caution Our retrospective study design may not offer the same level of rigor as a randomized controlled trial. Furthermore, the reproductive database did not provide detailed information on specific endometrial preparation methods (such as hormone replacement therapy or natural cycle), which could potentially influence implantation outcomes. Wider implications of the findings The freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, frozen embryo transfer is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option. Trial registration number KMUHIRB-E(I)-20210222

P-386 The effect of intravenous immunoglobulin versus placebo in patients with recurrent pregnancy loss: a systematic review and meta-analysis of randomized trials

Abstract Study question In women with recurrent pregnancy loss (RPL), how does intravenous immunoglobulin (IVIg) compared with placebo affect live birth rate (LBR) in the first subsequent pregnancy? Summary answer IVIg significantly improved LBR in the per protocol (PP), but not the intention to treat (ITT) analysis. LBR increased significantly with number of pregnancy losses. What is known already RPL is defined as two or more pregnancy losses before 24 weeks of gestation, impacting 1-2% of fertile couples. It results from diverse causes, and immunological factors are increasingly implicated in unexplained RPL cases. IVIg has been studied as a treatment with various proposed mechanisms. Existing research on IVIg in RPL has shown conflicting results, but a recent Japanese randomized controlled trial (RCT) reported a significantly increased LBR when IVIg was administered early and in high-dose. Study design, size, duration We conducted a systematic review and meta-analysis of relevant (RCTs, incorporating individual patient data (IPD) to evaluate IVIg’s impact on LBR in RPL patients. Participants/materials, setting, methods This study adhered to PRISMA guidelines and was registered in PROSPERO (ID CRD42023375788). We searched PubMed, Embase, and Cochrane libraries for relevant RCTs up to March 20, 2023. We conducted a meta-analysis with predefined primary (live birth and clinical pregnancy rates) and secondary outcomes. Risk ratios with 95% confidence intervals were calculated for dichotomous outcomes, and mean and standard deviation for continuous variables. We contacted the original authors to perform subgroup analyses based on IPD. Main results and the role of chance A total of 10 RCTs comprising 594 women were included in the meta-analysis, and IPD were retrieved from six RCTs including 354 women. No statistically significant results in LBR between IVIg and placebo treated women were found in the ITT analysis (RR: 1.02 [95% CI 0.86-1.22] p = 0.78). In the PP analysis, LBR was increased in the IVIg group compared with placebo (RR: 1.23 [1.00-1-50]). A statistically significant increase in clinical pregnancy rate was found in the IVIg group compared with placebo among women receiving high dose (median ³ 77.5 g) IVIg (RR: 1.79, [95% CI 1.21-2.65], p = 0.004). Furthermore, a statistically significant decrease in pregnancy loss rate was found in patients receiving high doses of IVIg (RR: 0.76 [95% CI 0.60-0.96], p = 0.02) compared to placebo. In the IPD analysis, RRs for live birth in the IVIg group compared with placebo increased steadily with the number of previous pregnancy losses. RRs for live birth in patients receiving IVIg compared with placebo were 5.26 (1.58-17.53) and 7.50 [1.20-47.05) in patients with ≥6 and ≥7 consecutive pregnancy losses, respectively. In analyses of IPD data adjusted for maternal age, the RRs for live birth were almost similar. Limitations, reasons for caution Limitations in the systematic review include potential bias due to financial support from pharmaceutical companies in half of the studies; potential confounding in subgroup analysis, missing individual patient data; and clinical and methodological heterogeneity among the included RCTs, which all may impact the overall reliability of results. Wider implications of the findings The findings highlight the importance of patient selection and personalized treatment. The PP analysis favored IVIg, emphasizing importance of protocol adherence. Secondly, the effectiveness of IVIg seems to increase with number of previous consecutive pregnancy losses. Thirdly, the dose of IVIg seem to impact its effectiveness. Trial registration number CRD42023375788

P-299 The influence of ovarian endometriomas surgery or not and the iron overload in follicular fluid on the outcome of IVF-ET

Abstract Study question To investigate the influence of ovarian endometriomas(OEM) surgery or not on the outcome of in vitro fertilization and embryo transfer. Summary answer Laparoscopic surgery can not significantly improve the outcome of IVF-ET in OEM patients, but may decrease the ovarian reserve. What is known already Despite the great advantages of ovarian endometriomas surgery treatment in endometriosis-linked infertility, the impact of laparoscopic cystectomy on outcomes of infertility management with ART is controversial. Numerous mechanisms have been proposed in an effort to delineate the multifaceted pathophysiology that induces impairment of reproductive dynamics in patients with OEM. Reactive oxygen species, dysregulation of the immune system and iron overload constitute the crucial mechanisms that detrimentally affect oocyte and embryo developmental potential. Study design, size, duration This study retrospectively included 882 cycles in our reproductive center from January 2018 to December 2020, and the patients were divided into operation group (n = 386) and OEM group (n = 496) according to whether they underwent laparoscopic cystectomy before IVF-ET. Participants/materials, setting, methods The baseline data of age, infertility duration, basic FSH, AFC, and BMI were used as matching factors, and Propensity score matching was carried out according to the sample ratio of 1:1, and 327 cycles in the operation group and 327 cycles in the OEM group were finally included. Follicular fluid was collected under ultrasound guidance during oocyte retrieval. A total of 74 follicular fluid samples meeting the study conditions were collected. Main results and the role of chance (1)The clinical pregnancy rate of fresh embryo transfer cycle in the OEM group was significantly higher than that in the operation group (77.4% Vs 52.9%), and the difference was statistically significant (P = 0.039). There was no significant difference in pregnancy outcome in frozen embryo transfer cycle (P &amp;gt; 0.05). (2) The results of Multi-factor logistic regression model showed the clinical pregnancy rate of patients in the OEM group was 3.048 times than that of patients in the operation group in fresh cycle, and the difference was significant (OR 3.029 95%CI 1.017-9.018, P = 0.047), while early abortion and live birth pregnancy outcomes were not significantly affected in both groups. For the frozen embryo transfer cycle, there were no significant effects on clinical pregnancy, early abortion and live birth pregnancy outcomes in both groups. (3) There was no significant difference in follicular fluid iron concentration between OEM group and control group(11.53±3.38 Vs 12.18±4.37μg/dl, P = 0.112). The concentration of ferritin in follicle fluid in OEM group (57.38±139.90) was significantly higher than that in control group (24.88±13.76 μg/ml), the difference was statistically significant (P = 0.032). Limitations, reasons for caution The present study being of a retrospective and monocentric study, may not come to a very convincing conclusion, and some unknown biases might still exist due to possible underestimation of some confounders. Wider implications of the findings Collectively, our results indicate that laparoscopic ovarian cystectomy couldn’t significantly improve the IVF-ET outcomes in patients with OEM, but rather increased the risk of reduced ovarian reserve function. Ovarian reserve function was the main factor affecting the IVF-ET outcomes for infertile patients with OEM. Trial registration number /

The effects of age, mature oocyte number, and cycle number on cumulative live birth rates after planned oocyte cryopreservation.

To examine the effects of age, mature oocyte number, and cycle number on cumulative live birth rates after planned oocyte cryopreservation (OC), with the goal of developing a patient counselling tool. We performed a retrospective cohort study of all patients with ≥ 1 autologous oocyte thaw at our university-affiliated fertility center before 12/31/2023. Patients were included if they (1) had a live birth or ongoing pregnancy > 12weeks from OC, or (2) used all oocytes and euploid/untested embryos from OC. Primary outcome was cumulative live birth / ongoing pregnancy rate (CLBR). 527 patients with 1 OC cycle, 149 patients with 2 OC cycles, and 55 patients with ≥ 3 OC cycles were included. Overall CLBR was 43%. CLBR was > 70% among patients who thawed ≥ 20 mature oocytes that were cryopreserved at age < 38years. Multiple logistic regression showed that age at first OC and total number of mature oocytes thawed independently predicted CLBR, but number of OC cycles did not. Patients must be counselled that younger age at OC and more mature oocytes improve CLBR. However, additional OC cycles do not independently improve CLBR. Our results can help patients decide whether to pursue additional OC cycles to obtain more oocytes.

The Effectiveness of Routine Cerclage in In Vitro Fertilization (IVF) Twins.

The incidence of twin pregnancies is on the rise worldwide due to assisted reproductive technologies. Cervical dilatation is a frequent complication and can be considered a cause of premature births in twin pregnancies. In vitro fertilization (IVF) twins are more prone to preterm delivery. Routine cervical cerclage with normal cervical length is not recommended in twins, but studies were not done on IVF twins. So, this study aims to evaluate the effectiveness of routine transvaginal cerclage in twin IVF pregnancies with normal cervical length on maternofetal outcome. A retrospective case-control study was conducted at a maternity hospital in eastern Indiafrom January 2016 to December 2019 with over 21800 deliveries. Two groups were taken, cases were those IVF twins with normal cervical length in whom cervical cerclage was done as they have referred to our hospital from the IVF centers for cerclage and in control no-cervical cerclage as they are referred from other IVF centers where cerclage was not a routine protocol. We have excluded cerclage done for history, ultrasound indicated, uterine anomalies, and monochorionic twins. Fifteen participants were recruited in both cases and controls. In our study 2 (6.66%), 4 (13%), and 26 (86%) were IVF twins delivered at a gestational age of <28 weeks, 28-32 weeks, and 32-37 weeks, respectively. The mean age of participants, mean gestation age at delivery, and birth weight in cases and control were 35.27 ± 5.98 years (min: 23; max: 45), 32.40 ± 5.54 years (min: 25; max: 44); 34 weeks 2 days ± 3.28 (min: 31; max: 37), 33 weeks 5days ± 1.66 (min: 25; max: 37); 1961.33 ± 340 gram, 1899.33 ± 437.48 gram, respectively with no statistical significant difference (p = 0.186, p = 1, p = 0.668, respectively) Conclusion: Routine transvaginal cerclage is not effective in twin IVF pregnancies with normal cervical length for preventing preterm births. IVF twin women usually present at a late age and their birth weight are also low.

Factors affecting implantation: What really matters?

Factors affecting embryo implantation, particularly in assisted reproductive technology, remain controversial and poorly understood. Better understanding and optimization of the process of implantation in assisted reproductive technology is important to improving live birth rate and pregnancy outcomes. In this literature review, we examine the key factors involved in implantation and elaborate on current practice, emerging data, and gaps in knowledge.

Endometriosis and risk of adverse pregnancy outcomes: a retrospective multicenter cohort study

To investigate first, the association between endometriosis and preterm birth; second, the associations between endometriosis and preeclampsia, placenta previa, postpartum hemorrhage, stillbirth, and small-for-gestational-age infants (assessed by birthweight); and third, the risk of these adverse pregnancy outcomes with and without the use of medically assisted reproduction. Multicenter retrospective cohort study. A total of 103 French maternity units. Deliveries by 368,935 women (377,338 infants) from 1999 through 2016. Endometriosis, defined as a single disease entity (endometriosis and/or ademyosis) MAIN OUTCOMES MEASURES: The main outcome was the preterm birth rate (both <37 and <33 weeks). The secondary outcomes were rates of preeclampsia, placenta previa, postpartum hemorrhage, stillbirth, and small-for-gestational-age neonates. Women in the endometriosis group had more frequent histories of infertility before the included pregnancy (34.7 vs. 5.0%), more hospitalizations during the pregnancy (27.4 vs. 19.8%), and more planned cesarean sections (14.0 vs. 8.7); they more often were nulliparous (51.7 vs. 43.4%). The prevalence of preterm birth at <37 weeks was 11.1% in the endometriosis group and 7.7% in the unexposed group, and for <33 weeks, it was 3.1% and 2.2%, respectively. The adjusted relative risk for confounding factors was higher in the endometriosis than the unexposed group for preterm delivery <37 weeks (1.40, 95% confidence interval, 1.18-1.67) or <33 weeks (1.53, 95% confidence interval, 1.08-2.16). For the secondary outcomes, the adjusted risk ratios for preeclampsia, placenta previa, postpartum hemorrhage, and small-for-gestational-age status of <10th and <5th percentiles were higher in the endometriosis group. The adjusted risk ratios for stillbirth and small-for-gestational-age status of <3rd percentile did not differ between the two groups, and those after stratification by medically assisted reproduction for preterm birth at <37 and <33 weeks did not differ statistically significantly between them, for the secondary outcomes, only the risk of placenta previa was higher in the medically assisted reproduction and non-medically assisted reproduction subgroups. Pregnant women with endometriosis had higher risks of preterm birth and other poor pregnancy outcomes than women without endometriosis.

Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa

BackgroundHypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes.MethodsWe conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120–129 and dBP < 80), stage 1 hypertension (sBP 130–139 or dBP 80–89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group.ResultsFrom May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes.ConclusionThe ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.

Association between prenatal phthalate exposure and ano-genital indices among offsprings in an Israeli cohort

BackgroundIn-utero phthalate exposure was shown to be associated with shortened anogenital distance (AGD) in male newborns, but findings among female are inconsistent. While phthalate exposure among pregnant women in Israel is widespread, no study has examined the association with offspring AGD. The objective of the current study was to investigate the association between maternal phthalates urinary concentration and offspring AGD at time of delivery among a birth cohort in Israel. MethodsWe measured spot urinary concentration of monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexylphthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) among women presenting to the delivery room at Shamir Medical Center in Israel. Birthweight, length and AGD were measured in all newborns using a standardized protocol. Each AGD measurement was adjusted to weight (ano-genital index). Confounders included socio-demographic characteristics, comorbidities and obstetrical history. Univariate and multivariate analyses assessed the associations between phthalates, confounders and AGD. ResultsOverall, 193 mother and infant were analyzed. All newborns were born at term and had normal Apgar scores. Mean maternal age was 32 ± 4.7 years old. Mean birth weight and pregnancy week were 3183 ± 498 g and 39 ± 1.3, respectively. Median (IQR) urinary phthalate concentration adjusted to creatinine (ug/g) were 3.96 (2.2–6.6), 1.22 (0.7–2), 10.84 (7–20.4), 6.36 (3.3–11.2) and 0.64 (0.4–1.1) for MBP, MBzP, MECPP, MEHHP and MEOHP, respectively. Univariate comparison showed a significant association between higher than median MBzP concentration, higher Ano-Fourchetal index (AFI: 4.4 vs. 4.1, p = 0.037) and Ano-clitoral index (ACI: 11.5 vs. 10.4, p = 0.032) in infants. Total urinary phthalates concentration ≥26.25 μg/g was significantly associated with smaller penile width index (3.5 vs. 3.7, p = 0.022), higher ACI (11.6 vs. 10.3, p = 0.013) and a trend towards significance for higher AFI (4.3 vs. 4.1, p = 0.055). Following multivariate linear regression only PWI remained significantly associated with total phthalate urinary concentration. ConclusionsMaternal urinary phthalates concentration at delivery were not associated with female AGD, but total urinary phthalate concentration were inversely associated with penile width.

Unveiling therapeutic potentials and exploring maternal-fetal health benefits of metformin in pregnancy: A scoping review.

This scoping review synthesizes evidence on metformin's use during pregnancy, encompassing diverse conditions like gestational diabetes, type 1 and type 2 diabetes, polycystic ovary syndrome (PCOS), and obesity. Metformin demonstrates comparable efficacy to insulin in gestational diabetes, positive outcomes in type 2 diabetes pregnancies, and potential benefits in reducing complications. The review highlights nuances in its effects across conditions, indicating advantages such as reduced risk of macrosomia and cesarean section in gestational diabetes. However, its prophylactic role in preventing gestational diabetes and associated complications remains inconclusive. In obese pregnant women, mixed results are observed, with potential benefits in reducing pre-eclampsia risk. Metformin shows promise in preventing preterm birth and late miscarriage in PCOS pregnancies. Categorizing patient subgroups is crucial for identifying advantages, especially in gestational diabetes and type 2 diabetes. Challenges arise from study heterogeneity, necessitating standardized indications for dosage, timing, and postpartum follow ups. Efforts to identify patient characteristics influencing metformin efficacy are crucial for tailored therapy. Although metformin emerges as a viable option in complicated pregnancies, comprehensive research, standardized protocols, and subgroup identification efforts will enhance clinical utility, ensuring evidence-based therapies and optimal maternal and fetal outcomes. Bridging existing knowledge gaps remains imperative for advancing metformin's role in pregnancy management.