Does extending vaginal progesterone administration from 5-6 days improve pregnancy outcomes in Day 6 (D6) frozen embryo transfers (FETs) in oocyte donation cycles? Prolonging the time of vaginal progesterone supplementation does not improve pregnancy outcomes after D6 FETs in oocyte recipients. Progesterone is critical for endometrial preparation prior to embryo transfer, but the optimal duration of administration remains unclear. D6 blastocysts are associated with poorer clinical outcomes compared to Day 5 (D5) blastocysts, potentially due to either intrinsic limitations in implantation capacity or a shifted window of implantation (WOI). Extending progesterone administration has been hypothesized to optimize the WOI for D6 blastocysts. This retrospective cohort study included 485 FETs performed in 420 oocyte donation recipients, conducted from January 2020 to December 2023 in a single IVF center. Participants were divided into two groups based on the duration of progesterone supplementation: 5 days (P + 5, n = 282) and 6 days (P + 6, n = 203). The study involved oocyte recipients undergoing single D6 blastocyst transfer following endometrial preparation with vaginal progesterone (800 mg/day). Outcomes were analyzed using univariate and multivariate tests, including logistic regression adjusted for estrogen type and endometrial thickness. Mean recipient age (±SD) was 43.5 (±4.24) years, mean BMI was 25.1, and mean endometrial thickness was 9.6 mm on the day of transfer. Good-quality blastocysts accounted for 35% of all transfers. Clinical outcomes, including biochemical (26.24% vs 26.60%, P = 1.00), clinical (21.99% vs 20.69%, P = 0.83), and ongoing pregnancy (14.54% vs 13.30%, P = 0.79), as well as live birth (14.18% vs 10.66%, P = 0.27) and miscarriage rates (7.45% vs 7.39%, P = 1.00), were all similar between 5 and 6 days of progesterone supplementation, respectively. Adjusted analyses confirmed these findings. The retrospective design warrants careful interpretation. Results are specific to vaginal progesterone in oocyte donation cycles and may not apply to other populations or progesterone delivery methods. Additionally, the D6 embryos analyzed were those that did not reach blastocyst by Day 5 (delayed, poor-prognosis, and typically transferred last), which likely biases outcomes toward lower live birth rates. Compromised outcomes following D6 FETs compared to those of D5 blastocysts, likely reflect the intrinsic limitations of slow-developing embryos rather than a misaligned WOI. As prolonged progesterone exposure did not improve outcomes, the WOI may be broader than previously assumed, particularly in oocyte donation programs, where superior embryo quality may mitigate synchronization drawbacks. This study was internally funded by the Eugin Clinic, with no external sponsorship. The authors declare no competing interests. NA.

Fetal and maternal outcome in the pregnancies of patients with systemic sclerosis and very early diagnosis of systemic sclerosis in France: a prospective study.

Background/Objectives: Prenatal Exome Sequencing (pES) has revolutionized prenatal diagnosis in fetuses with congenital anomalies. Although its performance is very promising, previous pES studies have mainly focused on diagnostic yield, often without considering the actual impact on ongoing pregnancies. In this study, we aim to (1) assess whether a prenatal molecular diagnosis can reliably predict the clinical features of the unborn child and (2) determine the gestational age (gw) at which ultrasound (US) findings are sufficient to support the pathogenicity of genetic variants detected by pES. Methods: We retrospectively selected 47 cases complicated by US anomalies that underwent Exome Sequencing (ES) and for which complete clinical assessment was available. A blinded reanalysis of ES data was performed, considering only prenatal features. Results: In our cohort, standard ES led to a molecular diagnosis in 43% of cases. The blinded reanalysis revealed that a complete or partial retrospective prenatal diagnosis was achievable in 95% of diagnosed cases. The mean gestational week at which US data would have supported molecular diagnosis was 22 + 5 weeks. The clinical follow-up confirmed a syndromic presentation in 21 out of 23 newborns and in all terminated pregnancies. Conclusions: Our study further confirms that pES is a valuable diagnostic tool for detecting genetic etiology in fetuses with congenital malformations. In most cases, pES results accurately predict the postnatal phenotype. However, the prenatal setting requires specific adjustments and precautions, and a negative pES result cannot be considered reassuring.

The purpose of this study was to compare oral estradiol valerate and estradiol transdermal gel for clinical pregnancy outcomes in patients undergoing frozen-thaw embryo transfer (FET). This was a prospective study performed between March 1, 2017 and October 30, 2019. Totally 244 HR FET cycles were included, with 123 cycles using oral estrogen tablets (oral group) and 121 applying estradiol transdermal gel (gel group). The primary aim of this study was to compare implantation (IR), clinical pregnancy (CPR), miscarriage (MR) and live birth (LBR) rates between the two groups. The secondary aim was to assess liver function, specifically measuring alanine transaminase (ALT) and aspartate transaminase (AST) levels at 12weeks of gestation. There were no significant differences in EPR, IR, and CPR between the two groups. Meanwhile, the gel group had a higher live birth rate (55.37% versus 51.20%, p = 0.302) and a lower miscarriage rate (5.79% versus 10.57%, p = 0.173) compared with the oral group, but statistical significance was not reached. The oral group had higher ALT (16.58 ± 6.13 versus 23.78 ± 7.17, p < 0.001) and AST (19.70 ± 3.58 versus 23.78 ± 7.17, p = 0.001) levels at 12weeks of gestation. Estradiol transdermal gel is a safe and feasible alternative for endometrial preparation in frozen embryo transfer cycles, yielding comparable ongoing pregnancy rates to the standard oral regimen.

IntroductionFolic acid is crucial for fetal development, particularly during early pregnancy. Studies suggest that high folic acid intake (≥800 µg/day) may be associated with a reduced risk of miscarriage. However, the impact of an 800 µg dose on pregnancy outcomes in women with prior pregnancy loss currently remains unclear.Methods and analysisWe will conduct a multi-centre randomised controlled study comparing 800 µg and 400 µg in women with previous pregnancy loss. The primary outcome is live birth. Secondary outcomes include early pregnancy loss, ongoing pregnancy at 24 gestation weeks, homocysteine (Hcy) reduction, maternal and perinatal outcomes. We plan to recruit 1116 women (558 women per group). Data analysis will follow the intention-to-treat principle and per-protocol. Subgroup analysis will be conducted based on Hcy levels, previous pregnancy losses and body mass index.Trial registration numberChiCTR2500100255.

Objective: This study aimed to evaluate the effectiveness of micro-TESE combined with ICSI in patients with non-obstructive azoospermia (NOA) who had a history of mumps orchitis, focusing on sperm retrieval rates, embryological development outcomes, and clinical pregnancy results. Materials and Methods: This retrospective study analyzed 293 patients with NOA who underwent micro-TESE, assessing sperm retrieval rates, hormone profiles, and subsequent embryological and clinical outcomes, with a particular focus on those with a history of mumps orchitis. Results: The overall sperm retrieval rate (SRR) among NOA patients was 59.4% (174/293). Remarkably, patients with a history of mumps orchitis (n=51) had a significantly higher SRR of 94.1% (p &lt; 0.05) than those with other etiologies. Additionally, SRR-positive patients exhibited significantly elevated levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (p = 0.022 and p = 0.015), suggesting a possible compensatory response of the hypothalamic–pituitary–testicular axis. Among the 48 ICSI cycles performed in the mumps orchitis group, the fertilization rate was 70.4 ± 22.7 %, the Day 5 blastocyst formation rate reached 60.4%, the β-hCG positivity rate was 82.8%, and the ongoing pregnancy rate was 69.0%. Conclusion: Micro-TESE combined with ICSI proves to be an effective and optimal treatment for NOA patients, especially those with a history of mumps orchitis, achieving high sperm retrieval and promising ongoing pregnancy outcomes. The findings also underscore mumps as a continuing threat to male fertility in Vietnam, reinforcing the importance of early diagnosis and timely medical intervention.

ABSTRACT Objective We aimed to identify independent predictors of ongoing pregnancy in patients undergoing mild-OS FET cycles, focusing on follicular phase characteristics and luteal support regimens. Methods In this multicenter, retrospective cohort study conducted between January 2021 and August 2024 across Bahceci in vitro fertilization (IVF) centers in Türkiye, 489 FET cycles with mild-OS using letrozole were analyzed. Biochemical and ongoing pregnancy outcomes were assessed in relation to demographic characteristics, ovarian stimulation parameters, ovulation triggering strategies, and LPS approaches. Multivariate logistic regression was used to determine independent predictors. Results The overall biochemical and ongoing pregnancy rates were 58.5% and 43.4%, respectively. Subcutaneous progesterone (with or without vaginal route) improved biochemical pregnancy rates compared to vaginal-only LPS (67.1% vs. 52.7%, p = 0.008), although this did not translate into significantly higher ongoing pregnancy rates. In adjusted models, only younger female age (OR = 0.94, 95% CI: 0.90 to 0.99, p = 0.01) and a higher number of embryos transferred (OR = 2.00, 95% CI: 1.16 to 3.45, p = 0.01) were independently associated with ongoing pregnancy. Follicular diameter, number of follicles >10 mm, estradiol and LH levels, or triggering with hCG did not significantly impact outcomes. Conclusion In mild-OS FET cycles, while subcutaneous progesterone support may improve early implantation outcomes, ongoing pregnancy is primarily influenced by female age and embryo number. These findings support a flexible approach to LPS and triggering in mild-OS protocols without compromising clinical success.

The role of myomectomy for intramural (IM) fibroids prior to artificial reproductive technique (ART) cycles is still debatable. This study assesses evidence regarding the effect of myomectomy for IM fibroids on invitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle outcomes. Online search of databases from June 1949 to February 2024 were performed. A literature search was performed using Ovid MEDLINE, EMBASE, and Cochrane Library databases. Medical subject headings and keywords were used to generate a subset of citations for myomectomy, fibroid, leiomyoma, assisted conception, ICSI, IVF, ART, and pregnancy outcomes. The PRISMA checklist was completed. RefWorks was used for reference management. Eligible studies were identified by two independent reviewers. Rayyan was used for data screening. RevMan v5 software was used for data screening, extraction, and synthesis. All women undergoing IVF/ICSI cycles with fresh or frozen embryo transfer with IM uterine fibroids were included. A total of 1572 studies were identified, with 423 assessed for eligibility, 118 duplicates removed, and 58 meeting the inclusion criteria. Seven studies were included in the systematic review. A total of 1644 women reported on in these seven studies. Results show a 63% higher chance of an ongoing pregnancy rate/live birth rate in those who underwent myomectomy compared to those who did not have myomectomy, prior to IVF (Relative Risk (RR)1.64 (1.15-2.33); P ≤ 0.01). This systematic review of non-RCTs has shown beneficial effects, although there is significant variation in reporting fibroids by International Federation of Gynecology and Obstetrics classification and on reporting of the outcomes; hence, further well-designed studies are required. Individualized patient care for the decision to undergo a myomectomy prior to IVF/ICSI should be considered.

This study aimed to determine the optimal timing of cryopreservation and biopsy procedures in preimplantation genetic testing for aneuploidy (PGT-A) by comparing clinical outcomes between fresh embryo biopsy (fresh biopsy) and frozen-thawed embryo biopsy (frozen biopsy) procedures in high-risk patients. This retrospective study included 844 patients undergoing 844 cycles conducted from August 2019 to December 2023. PGT-A was performed via trophectoderm biopsy using array comparative genomic hybridization and next-generation sequencing for comprehensive 24-chromosome screening. Patients were divided into two groups based on biopsy timing: fresh embryo biopsy (531 patients) and frozen- thawed embryo biopsy (313 patients). The clinical pregnancy rate was significantly higher in the fresh biopsy group compared to the frozen biopsy group (58.7% vs. 45.6%; odds ratio [OR], 1.695; 95% confidence interval [CI], 1.215 to 2.364; p=0.002). Furthermore, the fresh biopsy group showed higher implantation rates (45.6% vs. 32.1%; OR, 1.767; 95% CI, 1.274 to 2.451; p=0.002), ongoing pregnancy or live birth rates per cycle (48.0% vs. 35.8%; OR, 1.652; 95% CI, 1.177 to 2.319; p=0.004), and rates of good-quality blastocysts (57.1% vs. 32.1%, p<0.001) compared with the frozen biopsy group. Miscarriage rates did not differ significantly between the groups (18.2% vs. 21.4%; OR, 0.818; 95% CI, 0.457 to 1.465; p=0.501). Fresh biopsy demonstrated superior clinical outcomes compared with frozen biopsy, likely due to better embryo quality. Both fresh and frozen biopsies remain viable options for PGT-A, with frozen biopsy serving as a practical alternative. Embryo quality and euploid status continue to be critical considerations for embryo transfer selection.

The aim of this study is to evaluate the efficacy of prenatal second trimester ultrasound in diagnosing isolated congenital clubfoot and to assess the role of prenatal genetic testing. We conducted a retrospective cohort study in the North-West region of the Netherlands with prenatally suspected clubfoot between 16 and 24weeks of gestation from 2007 to 2021. We included isolated cases, defined as no additional structural anomalies on the initial targeted ultrasound. Rapid aneuploidy testing, chromosomal microarray analysis, and/or exome sequencing were performed via invasive testing following on parental request. We identified 423 cases of isolated clubfoot. The diagnosis changed to prenatal non-isolated clubfoot during prenatal follow-up in 20 cases (5%); in 10 cases during a follow-up ultrasound, and in 10 cases, an underlying genetic condition was found. In 11 cases, the initial suspicion of clubfoot was not confirmed at follow-up ultrasound. There were 387 ongoing pregnancies with a prenatal diagnosis of isolated clubfoot. In 47 children (12%), diagnosis changed postnatally to non-isolated. These postnatal findings were classified as major in 36 children (9%). In 40 cases (10%), the prenatal diagnosis of clubfoot was not confirmed postnatally. Prenatal ultrasound combined with genetic testing are components in the work-up of clubfoot, enabling the identification of associated structural anomalies and underlying genetic disorders. Despite advances in prenatal ultrasound and genetic testing, distinguishing isolated clubfoot from cases with additional structural or genetic anomalies remains challenging. Moreover, prenatal genetic testing does not exclude the absence of structural or neurodevelopmental issues diagnosed after birth.

Fetal microcephaly, defined as a small head circumference in utero or at birth, is a rare but clinically significant condition that may be associated with an increased risk of neurodevelopmental delay and impairment. However, the comprehensive analysis of multiple genetic testing methods for fetal microcephaly remains limited. This study aimed to summarize the clinical characteristics, ultrasound phenotypes, and genetic etiologies of prenatally diagnosed microcephaly. A single-center retrospective study was performed on fetuses with microcephaly. A total of 197 fetuses with microcephaly undergoing invasive prenatal diagnosis were recruited. Cytogenetic and monogenic abnormalities were investigated using karyotyping, chromosomal microarray analysis (CMA), copy number variant sequencing (CNV-seq) and whole exome sequencing (WES) were further analyzed. Among the 197 fetuses, 48.7% (96/197) had isolated microcephaly, while 51.3% (101/197) had non-isolated microcephaly. Within the non-isolated group, 24.9% (49/197) presented soft markers and 10.2% (20/197) exhibited structural defects. The incidences of chromosomal abnormalities (12.9%, 13/101) and pathogenic CNVs (6.9%, 7/101) were both higher in nonisolated fetuses than those in isolated fetuses. Significant differences were observed in the rate of chromosomal abnormalities across the borderline, moderate and severe microcephaly subgroups, and pCNVs were detected more commonly in the severe subgroup than in the borderline or moderate subgroup. Trio-WES, performed in 24 cases, revealed single gene variants including the POGZ gene, which was associated with the phenotype of microcephaly. The overall rate of adverse pregnancy outcomes was 33.1% (57/172), excluding ongoing pregnancies and cases lost to follow-up. Fetal microcephaly represents a genotypically and phenotypically heterogeneous disorder. The comprehensive application of multiple genetic testing approaches provides an effective and essential strategy for the prenatal diagnosis of the diverse etiologies underlying fetal microcephaly.

Does the storage duration of a single-step embryo culture medium within its labelled 1-year shelf-life affect embryo development, pregnancy outcomes, or birthweight in IVF? The age of a single-step embryo culture medium with a 1-year shelf-life is not associated with embryo development, cumulative live birth, or neonatal outcomes such as birthweight or preterm birth. Media composition, pH, and osmolality are recognized as important measures of media quality. In contrast, the shelf-life of culture media is poorly studied, resulting in different expiries among suppliers, with most between 120 days and 26 weeks. These differences have far-reaching implications, with the potential to affect success rates while increasing cost and waste. Most importantly, it is critical to know if 'old' media results in similar or worse IVF outcomes than 'fresh' media. A retrospective multicentre study was conducted using 9680 IVF/ICSI cycles from 6330 patients across eight clinics in Australia between October 2020 and December 2023. Inclusion criteria were autologous cycles with ≥1 fertilized oocyte and known media production date. Cycles using thawed oocytes/embryos or non-standard transfer days were excluded. All embryos were cultured in time-lapse incubators using single-step media. Cycle outcomes, including embryo development, cumulative pregnancy, live birth, preterm birth, and birthweight for singleton, were analysed using unadjusted and adjusted regression models, as well as generalized estimating equation models to account for repeated measures within same patients. Media age at use ranged from 38 to 365 days (mean ± SD: 190 ± 61 days). No statistically significant associations were observed between media age and embryo development outcomes, including percentage of Day 5/6 blastocysts (P = 0.389) and Day 5/6 usable blastocysts (P = 0.255). Similarly, media age was not associated with cumulative cycle outcomes including clinical pregnancy (P = 0.669), ongoing pregnancy (P = 0.986), or live birth (P = 0.257) in adjusted models. Subgroup analyses, including preimplantation genetic testing cycles and fresh transfers, yielded consistent results. Among 1070 singleton live births, media age was not associated with preterm birth (P = 0.818) or birthweight (P = 0.161). This was a retrospective study based on a single medium type; results may not generalize to other formulations. Post-opening media handling was not captured, which may introduce unmeasured variability. Prospective studies are needed to confirm these findings across diverse media types and settings. These results support more flexible use of culture media up to expiration and suggest longer shelf-life media can be used to reduce waste and logistical burdens. Broader application could support sustainability goals in IVF practice. No funding was attached to this study. D.M. has received consulting fees from Dawn-bio, Fujifilm Irvine Scientific and Overture Life; and speaker's fees from Genea Biomedx and Organon. The other authors declare no conflict of interest. N/A.

Abstract In Germany, follow-up after medical abortion is typically conducted via ultrasound examination. International evidence suggests that self-administered follow-up using low-sensitivity pregnancy tests may be a safe and acceptable alternative. This study assessed the effectiveness and acceptability of this approach within the German healthcare system. In this prospective, multicenter, partially randomized, patient preference study conducted in 11 German centers (March–September 2024) involving 312 women, participants with strong preferences could choose their preferred follow-up method, while all others were randomized to either self-testing or ultrasound follow-up. Follow-up was performed using a low-sensitivity pregnancy test (1000 mIU/ml) at home or by ultrasound examination in the clinic. The primary outcome was the detection of ongoing pregnancies; patient satisfaction was assessed as a secondary outcome. The detection rate of ongoing pregnancies was 100% in both groups. Specificity was 92.7% in the self-testing group and 100% in the ultrasound group. Complications were rare and occurred at similar rates in both groups. Discordant cases were rare and mainly represented false-positive results with faint test lines near the cut-off; severe complications did not occur more frequently. Satisfaction with the follow-up method was slightly lower in the self-testing group (85.9%) compared to the ultrasound group (98.3%) but remained within an acceptable range. Subjective feelings of safety were high in both groups. Self-administered follow-up using a low-sensitivity pregnancy test is a safe and well-accepted alternative to ultrasound examination after medical abortion. It may improve access to follow-up care, particularly for women living in underserved or remote areas.

Gestational weight gain (GWG), the maternal weight gained between pre-pregnancy and delivery, is an important risk factor for adverse maternal and infant health outcomes. In 1990, the National Academy of Medicine released GWG recommendations based on pre-pregnancy body mass index (BMI). These guidelines were revised in 2009, yet few studies have assessed temporal trends in GWG following the change. To evaluate temporal trends in total GWG within a large, ongoing pregnancy cohort. We used data from a prospective cohort in Boston, Massachusetts, of 3675 participants with deliveries between 2007 and 2019. Using 29,037 serial weight measures (median = 7/participant), we fit mixed-effect models to predict weight at delivery. Total GWG (kg) was defined as the difference between the model-predicted weight at delivery and self-reported pre-pregnancy weight. We categorised GWG as below, within or above the 2009 BMI-specific guidelines. We analysed proportional trends in GWG categories: (a) overall and (b) stratified by maternal characteristics (pre-pregnancy BMI, race/ethnicity, educational level and parity). We analysed trends in covariate-adjusted geometric mean (GMs) of GWG using multiple linear regression. The proportion of participants gaining weight within the GWG guidelines decreased from 46% in 2007-2008 to 24% in 2018-2019, which was driven by an increase in those gaining above the guidelines (40% to 73%). Across maternal characteristics, the largest increases of proportions above the guidelines were among those of normal pre-pregnancy BMI (19% to 62%) and of non-Hispanic Black (48% to 85%) or non-Hispanic White (37% to 74%) race/ethnicity. Consistently, GMs increased from 8.3 kg (95% confidence interval [CI] 6.3, 10.8) in 2007-2008 to 10.9 kg (95% CI 7.9, 14.9) in 2018-2019. Results from this large cohort study provide evidence that fewer women have been meeting the revised GWG guidelines and more have been gaining above the recommendations.

The posttranslational histone modification H3K9me3 is crucial for constitutive heterochromatin (cHC) and supports genome stability and gene regulation during development. This epigenetic mark persists in human sperm post histone-to-protamine transition and is transmitted to the embryo. Although H3K9me3 variability is linked to abnormal sperm parameters, its role in fertilization and embryo development remains unclear. Given its retention in sperm, aberrant H3K9me3 levels may underlie cases of unexplained male infertility. Investigate the variability of H3K9me3 levels in sperm from normozoospermic men and assess its association with early embryo development and IVF outcomes. H3K9me3 and histone H3 levels were quantified by Western blot in surplus sperm from 99 normozoospermic men undergoing IVF-treatment. Patients were stratified into quartiles based on the H3K9me3/H3 ratio. Pre-implantation embryo development was assessed by time-lapse imaging, focusing on nuclear precursor body (NPB) dynamics and morphokinetics. IVF outcomes were reported as cumulative biochemical and ongoing pregnancy rates per ovum pick-up and compared across H3K9me3/H3 quartiles. H3K9me3/H3 ratios exhibited substantial inter-individual variability among normozoospermic patients. Embryos from the third H3K9me3/H3 ratio quartile (Q3) demonstrated the highest proportion of zygotes with NPB clustering and faster, more consistent development through the first two cleavage divisions compared to other quartiles. A significant non-linear association was found between H3K9me3/H3 ratio and cumulative biochemical pregnancy rates: couples in the lowest quartile (Q1) had significantly reduced odds of biochemical pregnancy compared to Q3 (adjusted OR [95% CI]: 0.30 [0.09-0.97], p = 0.045). No significant association was found for ongoing pregnancy rates. This study reveals that sperm H3K9me3 levels vary among normozoospermic men and correlate with early embryo development and biochemical pregnancy rates following IVF. However, no significant association was found with ongoing pregnancy, suggesting that additional mechanisms may determine long-term pregnancy viability. The non-linear relationship between H3K9me3/H3 ratio and embryo development suggests an optimal range for this epigenetic mark. These findings highlight the potential influence of paternal epigenetic variation, undetectable by standard semen analysis, on embryo quality and IVF outcomes. Further studies in larger cohorts are warranted to confirm these findings and clarify underlying mechanisms.

To compare the effect of two different assisted hatching laser protocols thinning assisted hatching laser (TAH) vs drilling of assisted hatching laser (DAH) and non-assisted hatching control group (NAC) on clinical pregnancy and live birth rates in frozen thawed cleavage stage embryo transfer cycles. This study included 310 infertile patients who underwent frozen embryo transfer (FET) cycles from 2021 to 2022 at the ART Unit of the Medical Point Hospital of Izmir University of Economics, Izmir. Patients included in the study were those between 20 and 40 years of age, who had undergone frozen-thawed embryo transfer after 'freeze-all' protocols. The exclusion criteria were azoospermia and degenerated embryos. In TAH, laser thinning was performed by making 4-5 shots at a depth of 50% of the thickness of the zona pellucida (ZP). In DAH, the laser opening was made from the outer part of the ZP to the inner part. In the last group in NAC, assisted hatching was not performed. Clinical pregnancy and ongoing pregnancy rates were compared between the TAH, DAH and NAC cycles. There was no difference in terms of the age of the woman, the BMI and the sperm parameters in the three groups. There were no statistical differences between the groups in terms of the number of oocytes, embryos and the quality of the transferred embryos. Clinical pregnancy in thinning assisted hatching laser (TAH), drilling of assisted hatching laser (DAH), non-assisted hatching control group (NAC) cycles (38% vs 39% vs 45% p = 0.842, respectively.), ongoing pregnancy (34% vs 32% vs 39%; p = 0.670, respectively.) and live birth rates (34% vs 29% vs 35,4%; p = 0.586, respectively) were similar in three groups. In conclusion, no significant differences were found between the TAH, DAH and NAC groups in terms of ART outcomes.

Background: Considering the limited and conflicting data regarding prevalence and risk factors of osteoporosis (OP) in systemic sclerosis (SSc), we aimed at evaluating a large population of patients at several Italian institutions. Enrollment started in October 2024 and will end in October 2025. Materials and Methods: We are investigating the presence of OP in randomly selected subjects fulfilling the 2013 ACR/EULAR SSc classification criteria using a partially retrospective design. Exclusion criteria include ongoing pregnancy, cancer, metabolic bone diseases other than OP, and therapies interfering with bone health; exceptions are chronic kidney disease, anti-osteoporotic drugs, glucocorticoids (GC), and proton pump inhibitors. OP was defined as history of fragility fractures (FX) and/or of bone mineral density (BMD) values with T-scores &lt; -2.5 or Z-scores &lt; -2.0. BMD is evaluated using DXA scans within 12 months before enrollment or performed at enrollment. Demographic and anthropometric data, menopausal status, dietary calcium intake, Charlson Comorbidity Index (CCI), and concurrent medications are assessed. Sarcopenia, when detected with the SARC-F+EBM questionnaire, is evaluated with functional tests such as hand grip strength, chair stand test, and gait speed. A characterization of SSc is performed, including age at diagnosis, disease duration, and organ involvement. The cumulative SSc-related damage is expressed with the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI). We provide the results of the pre-planned interim analysis performed in April 2025; the final analysis is planned in October 2025. Results: The interim analysis focused on 315 patients, with a mean age at enrollment of 63.2±11.3 years. They were diagnosed with SSc at a mean age of 51.2±12.4 years and had been affected for a median time of 10 years (interquartile range - IQR 12). Females made up the majority (n = 292; 92.7%) of the cohort, with 266 (91.1%) having been postmenopausal for a mean time of 17.3±10.1 years. The mean BMI was 24.3±4.4 kg/m², and 16.8% of patients were sarcopenic. Dietary calcium intake was insufficient (&lt;700 mg) in 70.4% of cases, and optimal (&gt;1000 mg) only in 3.9%. Approximately 30% of patients were taking GCs. The mean CCI score was 3.7±1.6, suggesting a 10-year mortality risk of approximately 40%. The median SCTC-DI score was 3 (IQR 3). Our main finding was that OP affected 136 (43.2%) subjects: 84 (61.8%) had reduced BMD values only, and 52 (38.2%) had a history of FX. Conclusions: Our interim analysis showed that 43.2% of patients were affected by OP, suggesting a potentially high burden in SSc. To identify any predictive factors of OP in SSc, the final analysis will include correlations with SSc organ involvement, biochemical markers, densitometric values, sarcopenia, body composition parameters, and FX risk calculations with the DeFRA algorithm.

The expanding global use of assisted reproductive technology (ART) warrants rigorous evidence synthesis. This umbrella review (UR) evaluated the strength and validity of evidence on ART effects on reproductive, perinatal, and maternal outcomes. We searched five databases and reference lists (Inception to 15 June 2025) to identify systematic reviews with meta-analyses of randomized controlled trials (RCTs). For each extracted association, we performed a reanalysis using random-effects models, calculated the 95% prediction interval, heterogeneity, small-study effect, and evaluated excess significance bias. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR). The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system, and the strength of evidence was also evaluated on a grading scale. This study is registered with PROSPERO (CRD42024563290). The UR included 23 meta-analyses (200 associations from 109 RCTs), with 69.6% rated high quality. Regarding reproductive outcomes, high credibility of evidence showed that frozen embryo transfer (ET), compared with fresh ET, was associated with a reduced risk of ectopic pregnancy. Sequential ET significantly improved ongoing pregnancy rates relative to single blastocyst or cleavage-stage ET. Single ET, compared with double ET, reduced multiple births, but decreased live birth rate. Regarding perinatal and maternal outcomes, high-credibility evidence indicated that frozen ET, compared with fresh ET, was associated with increased birth weight of singletons, and a higher rate of large for gestational age infants and miscarriage, but a lower rate of small for gestational age infants in cumulative measures and ovarian hyperstimulation syndrome. While frozen ET significantly reduced the risk of preterm delivery, it paradoxically increased the rate of neonatal hospitalization. This UR delineates trade-offs between ART and reproductive, perinatal, and maternal outcomes. Clinical decisions should balance effectiveness against potential risks, with future research focusing on personalized treatment strategies.

ObjectiveIn this study, we investigated whether adding autologous platelet-rich plasma (PRP) to the culture medium affects embryo development and clinical outcomes in patients with recurrent implantation failure (RIF).MethodsThis study included 201 patients with previous RIF. Of these, 77 opted to receive the treatment and were assigned to the PRP group, and 124 declined and were assigned to the control group. In the PRP group, normally fertilized embryos were cultured in medium supplemented with 5% PRP, whereas embryos in the control group were cultured without PRP. Embryo transfer was performed on day 3 after evaluation of embryo quality. A comparative analysis was then conducted between the two groups, focusing on embryo quality and clinical outcomes.ResultsAlthough no significant differences were observed in fertilization or cleavage rates, the PRP group had a significantly higher proportion of good-quality embryos with at least six cells on day 3 than the control group. The clinical pregnancy and implantation rates in the PRP group were also significantly higher than those in the control group. Furthermore, the ongoing pregnancy rate was notably higher in the PRP group, and successful live births were achieved. Miscarriage rates were similar between groups.ConclusionIncorporating PRP as an additive into the culture medium improved embryo quality and increased implantation, clinical pregnancy, and ongoing pregnancy rates.

Background: Human chorionic gonadotropin (HCG) has an important role in maintaining early pregnancy and has been studied to improve pregnancy outcomes. Objective: This study aimed to assess the effectiveness of a single 5,000 IU dose of HCG in improving early pregnancy outcomes for women at risk of complications. Methods: This prospective study was conducted at the Salauddin Specialized Hospital, Dhaka, Bangladesh, from January 2023 to January 2024 on 120 pregnant women in the early stages of pregnancy at 6 weeks without cardiac pulsation and positive β-hCG levels. They were randomly divided into two groups: the HCG group (n=60), which received 5,000 IU of intramuscular HCG, and the control group (n=60), who received standard care. The main outcomes included ongoing pregnancy rates, miscarriage rates, positive HCG levels, fetal heartbeat detection at 8 weeks, and hormone levels measured on day 5 after the injection. Results: The ongoing pregnancy rates were higher in the HCG group compared to the control group (86.7% vs. 70.0%, p=0.03). The miscarriage rate was lower in the HCG group (13.3% vs. 30.0%, p=0.03). Those who received HCG also had a higher chance of fetal cardiac pulsation positivity (83.3% vs. 66.7%, p=0.04) and a lower incidence of threatened abortion (10.0% vs. 23.3%, p=0.05). Biochemical analysis revealed higher levels of β-hCG (&gt;1,500 IU/L; 91.7% vs. 71.7%, p=0.01) and progesterone (&gt;10 ng/mL; 83.3% vs. 65.0%, p=0.02). We found weak-to-moderate correlations (r=0.25–0.34, p&lt;0.05) linking HCG to positive outcomes, indicating its role in maintaining pregnancy. Conclusion: Administering a single dose of HCG significantly improved early pregnancy (at 6 weeks without cardiac pulsation and positive β-hCG levels) outcomes by providing better hormonal support and reducing complications. These results suggest that HCG supplementation may be helpful for women at risk of early pregnancy loss, though further large-scale studies are necessary. J Rang Med Col. 2025 Sep;10(2): 115-120