Abstract:Prepubertal exposure to gonadotoxic chemotherapy, such as cyclophosphamide (CY), poses a significant risk to long-term fertility by depleting ovarian reserve and impairing oocyte quality. Such treatments are commonly administered to young girls with cancer, and when these individuals later seek assisted reproductive technologies (ARTs), concerns arise regarding the developmental competence and cryotolerance of resulting embryos. Using a mouse model, this study evaluated the impact of prepubertal CY exposure (2 successive weekly doses of 75 mg/kg body weight at 2 weeks of age) on the cryosusceptibility of embryos derived via in vitro fertilization (IVF) at their reproductive phase. Oocytes were collected from superovulated females six weeks post-CY treatment and fertilized in vitro, and the resulting cleavage stage embryos were subjected to vitrification-warming. Embryo survival and quality were assessed by blastocyst formation, inner cell mass (ICM) proliferation in vitro, and the expression of key pluripotency markers (Oct4, Sox2, and Nanog). Results showed no significant differences between CY-exposed and control groups in terms of post-warming survival or marker expression. These findings suggest that maternal CY exposure during the prepubertal period does not adversely affect the cryo-resilience of IVF-derived embryos, offering reassurance for childhood cancer survivors seeking ART treatment. Lay summary:Chemotherapy given during childhood can harm future fertility, especially in girls who have not yet gone through puberty. One common chemotherapy drug, cyclophosphamide (CY), may reduce the number and quality of eggs in the ovaries. Cancer survivors may be more likely to need IVF (in vitro fertilization) or other fertility treatments, given the impact of the treatment on their fertility. In this study, a mouse model was used to understand whether early-life exposure to CY affects the ability of embryos (created through IVF) to survive freezing and thawing, a common part of IVF treatments. The study found that embryos from mice exposed to CY before puberty survived the freezing process just as well as those from unexposed mice. The quality and health of these embryos, measured by their development and important growth markers, were also similar. These findings provide hopeful news for young girls who receive certain types of chemotherapy, who may still have the option to use IVF in the future without increased risk of embryo damage during freezing.

The fallopian tubes are critical segments of the female reproductive tract and are essential for transporting gametes and embryos. It creates a conducive environment necessary for successful fertilization, early embryo development, and embryo transport. The cellular composition and function of the fallopian tube are tightly regulated by the sex hormones estradiol and progesterone. Therefore, any pathological/ metabolic condition or exposure to exogenous agents with the potential to alter endocrine levels can have a significant impact on fallopian tube function and health. This review summarizes the effects of medications, infections, pathological conditions, lifestyle choices, and environmental factors that can significantly impact the morphology, histology, cellularity, and functionality of the fallopian tube.

Glycogen synthase kinase 3 alpha (GSK3α) has emerged as a prospective target to develop male contraceptives. Global or testis-specific loss of GSK3α, but not GSK3β, results in male infertility. Previous studies demonstrated that the GSK3α-selective inhibitor BRD0705 induces reversible infertility in heterozygous mice. Here, we show that BRD0705 induces similar infertility in wild-type male mice. Fertility outcomes remain largely unaltered following superovulation in female mice mated with BRD0705-treated males. Further, no evidence of foetal resorption was observed in these females. Sperm count in treated mice were not altered; however, morphological defects appeared during their passage through the epididymis. The GSK3α inhibitor affected pathways related to the enzyme's catalytic activity in epididymal sperm. Phosphoproteomic analysis of sperm from inhibitor-treated mice showed that phosphorylation of over 50 proteins involved in motility, metabolism, and fertility, among others, were significantly altered. Among the highly hypophosphorylated proteins, four are likely substrates of GSK3 (viz., AKAP4, NT5C1B, SPATA18, and TRA2B). Analysis of the seminiferous tubules of BRD0705-treated mice showed normal spermatogenesis, suggesting that the drug did not affect developing spermatogenic cells. However, in vitro exposure of post-meiotic germ cells demonstrated their susceptibility to this inhibitor. BRD0705, therefore, shows only a non-genomic effect at the post-translational level. These findings support GSK3α inhibition via BRD0705 as a non-hormonal, on-demand and reversible male contraceptive strategy.

Objective: Obesity in women is known to be associated with compromised ovarian function. The oocytes are characterized by elevated cytoplasmic oxidative stress and poor cytoplasmic organization under such conditions, which might affect their tolerance to exogenous stresses such as the freeze-thaw process. This study investigates the cryosusceptibility of oocytes derived from mice with high-fat diet (HFD)-induced obesity. Methods: Three-weeks-old female mice were divided into a control group (fed a normal chow diet) and an obese group (fed with HFD for 12 weeks). Oocytes from both groups were subjected to vitrification and thawing. Post-thaw survival, reactive oxygen species (ROS) levels, mitochondrial and endoplasmic reticulum (ER) distribution, ER stress, and the maturation potential of GV stage oocytes were evaluated. Results: Despite increased lipid accumulation and higher ROS levels observed in the oocytes of obese mice, the post-thaw survival rate of GV oocytes was comparable between the groups. However, obesity induced alterations in mitochondrial and ER distribution. Additionally, MII oocytes derived from vitrified-thawed germinal vesicle (GV) stage oocytes of obese mice showed a significantly higher percentage of spindle defects. A notable increase in ER stress markers GRP78 and ATF4 was detected in frozen-thawed GV oocytes compared to the control group. Conclusions: These findings suggest that maternal obesity does not significantly affect the cryosurvival of oocytes, but it does compromise oocyte quality after vitrification, underscoring the need for optimized cryopreservation strategies in obese patients undergoing ART.

INTRODUCTION:Phosphodiesterases (PDEs) are a family of enzymes that regulate intracellular levels of cyclic nucleotides, such as cyclic adenosine monophosphate and cyclic guanosine monophosphate. PDEs are considered key modulators of cellular signaling processes, including those governing male reproductive health. Owing to the pivotal role played by PDEs in male reproductive health, pharmacologic inhibition of PDEs has gained substantial attention in improving male reproductive health. However, despite the potential therapeutic application of PDE inhibitors (PDEis) in this field, a comprehensive understanding remains limited of the PDE subtype-specific actions in male reproductive tissues, the potential off-target effects, and the long-term safety of PDE inhibition, emphasizing a critical gap in current knowledge. A systematic evaluation of existing evidence on the role of PDEs, as well as the therapeutic application of PDEis and their safety, is necessary for a better understating in the context of male reproductive and sexual health. OBJECTIVES:This narrative review aims to critically synthesize and highlight the current evidence on the function of PDEs in male reproductive organs and evaluate the clinical applications of PDEis as therapeutic agents in male reproductive health and sexual medicine. METHODS:A comprehensive literature search was conducted in PubMed and Scopus to identify the expression and function of PDEs in male reproductive organs and the use of PDEis for the treatment of erectile dysfunction and reproductive cancer and for the improvement of male fertility. RESULTS:PDEs of different families are expressed in a tissue-specific manner in the testis, epididymis, prostate gland, seminal vesicle, and penis, indicating their significant role in male reproductive health. Inhibitors of PDEs, even though popularly known for their therapeutic role in treating erectile dysfunction, have exhibited a promising role in the treatment of prostate cancer, testicular cancer, testicular function enhancement, and sperm motility improvement. CONCLUSIONS:PDEis have a promising role in improving male reproductive and sexual health. However, the lack of studies addressing their long-term health effects and safety limits their routine therapeutic applications for improving male reproductive health. Future systematic clinical trials and mechanistic studies can certainly illuminate the possible role of PDEis in improving male reproductive health.

The fallopian tube microenvironment supports gamete transport, fertilization and early embryo development. Any disturbances in this microenvironment can lead to fertilization failure, infertility or ectopic pregnancy. In this study, we systematically investigated the effects of clomiphene citrate (CC) on human PAX8-positive fallopian tube secretory epithelial cells (hPFTSECs) to assess CC-induced alterations in the tubal microenvironment. Human fallopian tube tissues obtained from women undergoing postpartum tubectomy were enzymatically digested, and the isolated hPFTSECs were cultured with CC. CC exposure reduced hPFTSEC viability, clonogenicity, proliferation and organoid forming efficiency while inducing apoptosis, DNA damage, and senescence in a dose-dependent manner. Further, delayed cell-cycle progression and impaired DNA replication were observed in CC-exposed hPFTSECs. CC when administered to adult female Swiss albino mice, both single-dose (25, 50, and 100 mg/kg; intraperitoneally) and multiple-dose (10 mg/kg; intraperitoneally for four consecutive days) exposure caused several oviductal abnormalities, including epithelial disorganization, loss of ciliation, dysplasia, and hyperplasia. Our findings reveal that CC induces a spectrum of cytotoxic, genotoxic, and structural alterations in the fallopian tube epithelium, with potential implications for tubal function impairment and disruption of the optimal microenvironment essential for fertilization and early embryo development, which might negatively impact overall reproductive outcomes.

Context Women with obesity or polycystic ovary syndrome (PCOS) often require repeated ovulation induction (OI) due to ovulatory dysfunction and infertility. However, the cumulative effects of repeated stimulation on ovarian function and embryo development remain poorly understood. Aims The present study aimed to understand the consequences of repeated OI and/or repeated superovulation (SO) on preimplantation embryonic development in obese (high-fat diet-induced) and PCOS (high-fat diet and dehydroepiandrosterone-induced) mouse models. Methods Control (without any metabolic disorder), obese, and PCOS mice were divided into three experimental groups. The mice in one round of superovulation (SO1) were injected with 5 IU intraperitoneal (i.p.) injection of pregnant mare serum gonadotropin, followed by 10 IU of human chorionic gonadotropin 48 h later. In the repeated superovulation (SO3) group, mice were subjected to three rounds of superovulation with a gap of 9 days between each superovulation. Mice in the OI3 + SO3 group were administered with three doses of CC (50 mg/kg body weight, i.p., gap of 9 days between each CC injection), followed by three rounds of superovulation. Key results Both single and three rounds of superovulation resulted in decrease in primordial follicles and a moderate increase in atretic follicles in obese and PCOS mice. Reduction in the number of ovulated oocytes, increased rate of abnormal fertilization, decrease in blastocyst rate and elevated DNA damage in blastocysts were observed in in vitro fertilization-derived embryos. Conclusions These findings demonstrate compromised embryonic development following repeated ovarian stimulation. Implications The study highlights need for mild ovarian stimulation strategies in metabolically compromised patients undergoing infertility treatments.

Sperm preparation media used in assisted reproductive technology (ART) laboratories typically contain single or combined buffers to maintain pH and support spermatozoa homeostasis. Concerns exist that zwitterionic buffers, such as 4-(2-hydroxyethyl)-1-piperazine ethane sulfonic acid (HEPES) and 3-(N-morpholino) propane sulfonic acid (MOPS), may negatively affect intrinsic cellular functions. Hence, this prospective study evaluated the impact of various buffers on sperm selection by swim up from fifty-four sub-fertile men, which were then divided into normozoospermic samples (n = 27) and non-normozoospermic (n = 27) cohorts. Each ejaculate was split into six aliquots, and swim-up was performed with media buffered by bicarbonate, HEPES, MOPS, bicarbonate + HEPES, or bicarbonate + MOPS. Post-swim-up spermatozoa were assessed for motility, morphology, kinematics, acrosome reaction, mitochondrial integrity, and DNA damage. Bicarbonate-buffered medium yielded spermatozoa with significantly higher motility and mitochondrial activity in both normozoospermic and non-normozoospermic samples (p < 0.001). In contrast, media containing HEPES or MOPS were associated with reduced motility (p < 0.001), compromised sperm kinematic parameters (p < 0.05), and diminished mitochondrial potential (p < 0.05). The study findings highlight the importance of bicarbonate buffer over zwitterionic buffers in sperm preparation media for the selection of better spermatozoa during ART procedures

Oxygen concentration declines from 5–8% in the fallopian tube to ~ 2% in the uterine cavity. However, clinical studies investigating ultra-low O₂ concentrations (2–3%) during human embryo culture have reported conflicting developmental outcomes. Whether these developmental differences are accompanied by metabolic adaptation in human embryos remains unknown. In this preliminary prospective sibling-split oocyte study, 111 embryos from 13 patients were cultured under constant 5% O₂ or a physiological 8%–5%–2% O₂ gradient. Spent culture media (n = 222) were analysed by nuclear magnetic resonance spectroscopy and high-performance liquid chromatography–tandem mass spectrometry against matched incubated control media. Spent-media analyses confirmed embryo-derived metabolic activity, characterized by pyruvate and glutamic acid depletion together with alanine and glutamine secretion. Neither patient-level analyses nor embryo-level linear mixed-effects models identified statistically significant metabolomic differences between the two O₂ culture conditions, whereas metabolite-turnover patterns showed significant inter-patient variability. Blastocyst-forming embryos exhibited lower total amino acid turnover than arrested embryos in cleavage-stage media (P = 0.037), whereas a similar trend in blastocyst-stage media was not significant (P = 0.106). These findings suggest that patient-specific and developmental factors contribute to embryo metabolic variability, while subtle O₂-associated metabolic effects cannot be excluded. Given the limited sample size, these findings are preliminary and hypothesis-generating.

Abstract Genetic factors contribute to poor ovarian response (POR) in assisted reproductive technology cycles, with estrogen receptor gene polymorphisms ( ESR1 and ESR2 ) being explored as a causative factor in many studies. However, there is no systematic review and meta-analysis conducted on these studies to assess the association of these receptor polymorphisms on POR. This systematic review and meta-analysis evaluated the association between ESR1 and ESR2 single nucleotide polymorphisms (SNPs) and ovarian response in women undergoing controlled ovarian stimulation (COS). The study was registered with PROSPERO and conducted according to PRISMA guidelines. 11 eligible studies were included. Among the various SNPs, meta-analysis focused on ESR1 rs2234693 and rs9340799, and ESR2 rs4986938. ESR1 rs2234693 C‑allele carriers showed significantly increased odds of POR in both heterozygote (pooled log odds ratio (LOR) = 0.99, standard error (SE) = 0.213; odds ratio (OR) = 2.69, p < 0.001)) and dominant models (LOR = 1.69, SE = 0.449, OR = 5.41, p < 0.001), with consistent findings in European populations. Associations for ESR1 rs9340799 and ESR2 rs4986938 with POR showed substantial heterogeneity. Overall, ESR1 rs2234693 may be associated with POR, in women undergoing COS. Further large-scale studies with appropriate study designs are warranted to clarify the potential role of ESR polymorphisms in COS outcomes.

Hormonal signals intricately regulate breast growth and development. Any perturbations due to altered endocrine and metabolic conditions, such as in polycystic ovary syndrome (PCOS), may influence breast cancer risk. This review highlights the susceptibility of women with PCOS to breast cancer, with a focus on the potential contribution of its comorbidities, such as hyperandrogenism, obesity, insulin resistance, diabetes, menopausal status, inflammation, and use of ovulation induction agents to this association. This is a narrative review including articles and information collected from PubMed, Scopus, Google Scholar, and the World Health Organization (WHO) websites. Studies were selected based on the availability of an abstract and research publication in English. Reports related to PCOS, its characteristics (hyperandrogenism, hyperinsulinemia, insulin resistance, type 2 diabetes, obesity), fertility treatment, and their association with breast cancer were included. The interrelation between PCOS and breast carcinoma remains ambiguous due to inconsistent and inconclusive epidemiological evidence. The comorbidities associated with the condition are reported to collectively or individually influence this association. Women with PCOS present anovulatory cycles and have a high necessity of undergoing ovulation induction, further altering hormonal dynamics. Evidence in the literature suggests that the number of treatment cycles, age at the onset of treatment, and cumulative doses of agents used for ovulation induction are a few other factors that could affect breast cancer risk, though the results are inconclusive. Existing literature suggests that PCOS and its characteristics may impact the process of breast development and possibly contribute to breast cancer, although the evidence is still conflicting. Moreover, temporary alterations of endocrine profile following fertility medications may have a significant influence on the breast cancer risk, although research has shown inconclusive evidence. Hence, robust experimental studies are required to understand the underlying mechanisms and the long-term health implications for women with PCOS due to the intricate association between these factors. Few studies suggest that an altered metabolic and endocrine profile in PCOS women predisposes them to breast cancer. However, current epidemiological evidence is inconclusive in establishing a strong link between PCOS and the risk of breast cancer. As PCOS women often depend on assisted reproductive technologies for infertility treatment, ovulation induction/ controlled ovarian stimulation protocols may further increase the health risks. The present article is a comprehensive overview highlighting the possible association with breast cancer risk in PCOS women undergoing assisted reproduction.

Haploid parthenogenetic embryos (HPEs) typically exhibit poor in vitro development, which may be attributed to the absence of paternal factors. Since the metabolic pattern determines the developmental potential of early embryos, the present study aimed to ascertain whether the compromised developmental potential of HPEs reflects distinct metabolic requirements compared to normally fertilized embryos (NFEs). The developmental trajectories and utilization of key metabolic substrates of HPEs and NFEs of Swiss albino mice were assessed by culturing them in M16 medium with varying concentrations of glucose (0–5 g/L) and pyruvate (0–90 mg/L). mRNA expression of glucose transporter-4 (Glut-4), glycolytic [glucose-6-phosphate dehydrogenase (G6pd) and pyruvate dehydrogenase (Pdha1)] and antioxidant [superoxide dismutase (Sod1), catalase (Cat), glutathione s- transferase (Gstcd) and glutathione reductase (Gsr)] enzymes were assessed at various developmental stages. Higher blastocyst rate was obtained when HPEs were cultured in elevated glucose (5 g/L) and pyruvate (54 mg/L) concentrations. Inhibition of glycolysis using 2-deoxy glucose resulted in high percentage of HPEs getting arrested at 2-cell stage, while NFEs were able to progress to 4-cell stage. Spent media analysis revealed that HPEs exhibit high glucose dependency compared to NFEs. Further, G6pd, Pdha1, Sod1 and Cat were upregulated, while Gsr and Gstcd were downregulated in HPEs. Our findings suggest that the HPEs have altered metabolic requirements compared to NFEs and provide an insight into the paternal contribution in regulation of metabolic pathways in early embryos. This study forms a basis for optimizing culture conditions for in vitro development of parthenogenetic embryos.

Amino acids are vital biomolecules that can provide important insights into sperm functional competence. However, the level of amino acids (AAs) in seminal plasma and their implications on sperm characteristics remain less understood. For the first time, high-performance liquid chromatography (HPLC) in combination with a laser-stimulated fluorescence (LSF) system was used to profile AAs from the seminal plasma of 30 normozoospermic and 51 nonnormozoospermic ejaculates. Sperm characteristics, along with DNA integrity, were assessed and correlated with individual AAs. The HPLC-LSF system was able to detect a total of 18 AAs in the seminal plasma. A significant variation was observed between the two groups for all AAs (p < 0.05), except for aspartate. Notably, the relative intensities of AAs were significantly lower in the non-normozoospermic group. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) further highlighted distinct clusters based on the AA profiles of the two groups. The pathway analysis indicated differences in the metabolic pathways between the normozoospermic and nonnormozoospermic groups. The HPLC-LSF platform could serve as a potential tool in identifying seminal plasma AA levels. The low relative abundance of AA in the non-normozoospermic men could be attributed to aberrant metabolic pathways, underscoring their significance in male infertility.

Oocyte in vitro maturation (IVM) and vitrification are being considered as fertility preservation strategies for prepubertal cancer patients. Since prepubertal oocytes have differential sensitivity and response to vitrification compared to adult oocytes, there is a need to optimize the technique to improve the outcome. This study specifically looked into the effect of varying equilibration time and temperatures on the survival and functional competence of prepubertal mouse oocytes. Germinal vesicle (GV) stage and in vitro matured, metaphase II stage sibling oocytes retrieved from 2-week-old Swiss albino mice were equilibrated at 24 °C and 37 °C for 10 and 15 min during vitrification. GV vitrified-IVM (GVV) and GV IVM-vitrified (MIIV) oocytes that survived post-warming were assessed for mitochondrial potential, spindle integrity, spindle checkpoint transcripts, and DNA integrity. The GVV oocytes equilibrated at 37 °C for 15 min had a significantly lower maturation rate (P < 0.01). Survival was reduced when MIIV oocytes were equilibrated at 37 °C, regardless of equilibration duration (P < 0.05). The meiotic spindle and DNA integrity were affected at 37 °C/15 min equilibration (P < 0.01). IVM prepubertal mouse oocytes are at higher risk of experiencing cryo-damage with 37 °C equilibration. Hence, fertility preservation protocols must be refined and individualized for prepubertal age to safeguard the genetic and functional integrity of such oocytes.

JQ1, a small cell-permeable molecule is known for its potent inhibitory action on bromodomain and extraterminal (BET) proteins. Although earlier studies have shown its inhibitory effect on male gametogenesis, limited information is available about its influence on oocyte development. Since BET genes are known to exhibit regulatory functions on oocyte development and maturation, the present study aimed to investigate the effect of JQ1 on oocyte developmental competence under in vitro conditions. Germinal vesicle (GV) stage oocytes were collected from adult Swiss albino mice and subjected to in vitro maturation (IVM) in the presence of various concentrations of JQ1 (25, 50, and 100 μM). The metaphase II (MII) stage oocytes were assessed for cytoplasmic organization and functional competence at 24 h after IVM. A significant decrease in nuclear maturation (at 50 and 100 μM), symmetric cytokinesis, altered distribution of mitochondria and cortical granules, poorly organized actin and meiotic spindle, misaligned chromosomes, and elevated endoplasmic reticulum (ER) stress and oxidative stress was observed in JQ1-exposed oocytes. Presence of N-acetyl cysteine (NAC), in IVM medium resulted in significant reduction in JQ1-induced oxidative stress and symmetric cytokinesis. Administration of JQ1 (50 mg/kg, intra peritoneal) to adult Swiss albino mice primed with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) did not affect the ovulation. However, a high degree of oocyte degeneration, elevated intracellular reactive oxygen species (ROS), and GRP78 expression was observed in JQ1-administered mice. In conclusion, our study reveals that BET inhibitor JQ1 has detrimental effects on oocyte function and development.

A small multiple-dose regimen of cyclophosphamide (CY) compared to a large single dose in prepubertal mice has shown reduced follicle loss and improved fertility outcomes at early reproductive age. However, the long-term effects on the competency of oocytes from such surviving follicles, compared to those at post-pubertal age, remain unknown. Small multiple CY (75 mg/Kg, four weekly doses) injections were administered to prepubertal (PP75X4) and adolescent (AD75X4) Swiss albino female mice. At 22 weeks of age, surviving females were assessed for follicular pool and oocyte functional competency. The resulting embryos were assessed for blastulation, total cell number (TCN) quality, and in vitro inner cell mass (ICM) progression. At 22 weeks of life, PP75X4 females had a three-fold reduction (p < 0.001) in the total number of follicles compared to the untreated control. However, the differences between PP75X4 and AD75X4 were not statistically significant. Though PP75X4 females demonstrated a significant (p < 0.001) reduction in oocyte yield when compared to AD75X4, embryo quality, blastulation, TCN, and apoptosis were comparable between PP75X4 and AD75X4 groups. Small multiple doses of CY lead to reduced oocyte yield in prepubertal mice compared to adolescents. This study suggests that oocytes from prepubertal and adolescent individuals receiving small multiple doses of CY exhibit comparable functional competence, resulting in embryos of similar quality.

Over the past four decades, reports have emphasized the spatial and temporal trends in human semen quality and other markers of male reproductive health, which have sparked significant debate among fertility professionals. This trend appears limited to specific geographical regions rather than being global. The study aimed to retrospectively review the comprehensive distribution of semen characteristics and analyze their temporal changes over a period of 17 years at a single center in the southern parts of India. Ejaculates of 12,151 sub-fertile men undergoing infertility workup at the University Andrology Laboratory from 2006 to 2022 were included. Semen analysis was performed as per the World Health Organization (WHO, 1999, 2010) recommendations. The primary outcome of interest was temporal changes in semen parameters, whereas data regarding the distribution of semen characteristics were also measured. Sperm concentration, total sperm number, motility, vitality, and morphology showed no significant variations over time. The fifth percentile of semen volume, sperm concentration, total motility, vitality, and normal morphology were 0.5 mL, 1.5 million/mL, 21.0%, 28.0%, and 7.0%, respectively. This study revealed no temporal decline in sperm concentration, motility, and morphology in 17 years, and found fifth percentile sperm characteristics were lower than WHO reference values, marking the extensive long-term semen quality analysis from a single Indian laboratory. The findings reported here do not support an alarming temporal decline in semen quality.

Congenital anomalies (CAs) are a leading cause of perinatal and child mortality. With the increasing use of assisted reproductive technology (ART), there is a growing need for research on the health outcomes of children conceived through ART. This systematic review was performed to assess the incidence of CAs in ART-conceived children compared to those conceived naturally. This review followed the PRISMA 2020 guidelines and was registered with PROSPERO. A total of 113 studies were included in this meta-analysis, comprising 768,929 children in the ART group and 40,709,337 children in the control group which comprised spontaneously conceived (SC) children. The primary findings indicated that ART-conceived children have a marginally higher risk of CAs compared to the control group. Subgroup analyses showed that children conceived via ICSI, Day 3 transfer, and fresh embryo transfer (ET) had a slightly higher risk of CAs than those conceived via IVF, Day 5 transfer, or frozen embryo transfer (FET). The study highlights a slightly increased incidence of CAs among ART-conceived children over SC children, underscoring the importance of improving ART methods and closely monitoring the health of these children to reduce the risk of CAs.

Ovarian response is crucial in assisted reproductive technology, and mature oocyte retrieval is directly linked to higher live birth rates. Poor ovarian responders (POR) experience limited stimulation outcomes that contribute to significant cycle cancellations. Managing POR involves tailored protocols, yet no single approach has been universally validated as the most effective. Addressing this challenge, the Indian Fertility Society (IFS) developed comprehensive evidence-based guidelines for the diagnosis and management of POR. Using the PICO framework, a Guideline Development Group (GDG) conducted a comprehensive literature review across major databases up to October 31, 2023. Key outcomes included efficacy, safety, and patient-related measures. The GDG employed the GRADE approach to assess the quality of evidence and risk of bias. Recommendations were formulated based on the strength of evidence, benefit-harm balance, feasibility, stakeholder acceptability, and resource implications. The resulting evidence-based recommendations (EBRs) reflect the certainty of evidence and consensus among GDG members. The guidelines offered 44 EBRs (33 strong and 11 conditional) addressing 37 key questions to guide the management of POR. Among the EBRs, 1 was based on high-quality evidence, 6 on moderate-quality evidence, 25 on low-quality evidence, and 8 on very low-quality evidence and lack of evidence with recommendation for further research in 4. Most of the EBRs were based on low or very low-quality evidence, underscoring the need for further research. These guidelines prioritize patient safety and improve clinical outcomes, offering actionable insights into POR diagnosis and treatment protocols. Anti-Müllerian hormone and antral follicle count are reliable predictors for identifying patients at high risk of POR. The Corifollitropin alfa offers a comparable alternative to traditional gonadotropins. These guidelines serve as a valuable resource for assisted reproductive technology professionals by promoting a structured approach to managing POR and highlighting areas for future research.