Oestradiol and reproductive outcomes in ART: when too much of a good thing hurts
Oestradiol plays a crucial role in reproduction, particularly in assisted reproductive technology (ART), where it can reach supraphysiological concentrations. These fluctuations occur during ovarian stimulation in fresh embryo transfer cycles and during endometrial preparation for frozen embryo transfer, potentially impacting implantation and perinatal outcomes. Oestradiol influences endometrial proliferation, receptivity, implantation and placentation, with the sensitivity of the endometrium to systemic oestrogen emerging as a key determinant of reproductive success. In fresh embryo transfer cycles, ovarian stimulation induces histological, immunological and genetic changes in the endometrium, correlating with elevated oestradiol concentrations and possibly disrupting implantation. However, this adverse effect appears time-limited, as endometrial receptivity is restored in subsequent cycles. In FET cycles, both the duration and intensity of oestradiol exposure are critical, as excessive or prolonged exposure to exogenous oestradiol may impair reproductive outcomes. Despite these potential effects, strategies to regulate oestradiol concentrations in ART remain underexplored. This review examines the physiological and pathological roles of oestradiol in natural and ART cycles, emphasizing its impact on endometrial function, implantation and pregnancy outcomes. It highlights the need for further research to define optimal oestradiol thresholds and develop personalized ART protocols that consider both oestradiol concentrations and endometrial sensitivity to improve reproductive success and obstetric outcomes. Finally, it highlights strategies aimed at modulating oestradiol exposure to optimize reproductive success.
Effect of constant (5%) versus gradient (8%-2%) oxygen concentration on sibling human blastocyst development
Does a gradient of oxygen concentration, decreasing from 8% to 2% during prolonged embryo culture, yield a higher percentage of morphologically optimal blastocysts compared with a static 5% oxygen atmosphere?
Fertility preservation in endometriosis: evaluating surgical risks and emerging preservation approaches
Endometriosis poses significant challenges for women of reproductive age, particularly due to its impact on ovarian reserve and fertility. In addition to endometriosis-associated infertility contributing to diminished ovarian reserve by inflammation and oxidative stress, surgical interventions, often required to manage endometriosis, can exacerbate ovarian damage, further complicating fertility preservation. This narrative review critically examines the interplay between endometriosis treatment and fertility preservation strategies, offering insights into current surgical risks and emerging approaches to mitigate their impact on reproductive potential. Furthermore, it explores traditional fertility preservation methods, including oocyte, embryo and ovarian tissue cryopreservation, alongside advances in vitrification techniques that enhance success rates. Innovative minimally invasive surgical techniques, such as carbon dioxide laser vaporization, plasma energy ablation, haemostatic sealants, and robotic-assisted laparoscopy, are evaluated for their ability to preserve ovarian tissue. Moreover, emerging trends, including the use of artificial intelligence for personalized treatment planning and bioengineering innovations, such as three-dimensional-printed ovarian scaffolds, are discussed as transformative solutions for restoring fertility. A multi-disciplinary, patient-centred approach is emphasized, integrating expertise from gynaecology, reproductive endocrinology, and bioengineering to optimize fertility preservation outcomes. By bridging technological advances and clinical practice, this review aims to provide a framework for preserving fertility while addressing the complex challenges of endometriosis.
Assisted reproductive technology in Latin America: the Latin American Registry, 2022
What are the trends and effects of assisted reproductive technology (ART) interventions on the effectiveness and safety of ART carried out in Latin America during 2022.
Does systemic LH concentration influence live birth rate in programmed single euploid frozen embryo transfer cycles?
Does systemic LH concentration influence live birth rate (LBR) in programmed single euploid frozen embryo transfer (seFET) cycles?
Effects of infertility duration and aetiology, parental factors and ART on the risk of congenital anomalies: a comprehensive review
Infertility, affecting one in six people, represents an important global public health issue. Assisted reproductive technology (ART) provides effective treatment options, but concerns remain regarding its safety, particularly in relation to the potential risk of congenital anomalies. This literature review aims to synthesize current evidence on the association between infertility, ART and the occurrence of congenital anomalies. A comprehensive search of the MEDLINE, PubMed and Embase databases was made. In total, 727 references were obtained according to the search criteria. The full text of 393 articles was evaluated, and 143 articles were included in the review. The literature indicates increased risk of congenital anomalies both in individuals with infertility and in those who conceived using ART. Assessing the risk of congenital anomalies in the context of ART is complex due to the presence of numerous confounding factors, some of which are linked to parental characteristics. Notably, some types of congenital anomaly, such as congenital heart defects, genitourinary anomalies and genetic disorders, are reported more frequently in association with ART. In conclusion, the current literature suggests increased risk of congenital anomalies associated with ART. This underscores the need for further research to elucidate the underlying mechanisms and inform clinical strategies aimed at reducing this risk.
Investigating phototoxicity of optical coherence tomography imaging in porcine and human spermatozoa
Does exposure to near-infra-red optical coherence tomography (OCT) laser radiation induce phototoxic effects in porcine and human spermatozoa?
Disentangling the current role of LH activity in assisted reproduction: from biology to patient personalization
The importance of determining the precise role of gonadotrophins in assisted reproductive technology (ART) is increasingly recognized, as optimizing ovarian stimulation protocols is crucial for improving outcomes. Recent advances in reproductive biology highlight the multifaceted functions of LH, revealing a complex interplay between its endocrine actions and local ovarian mechanisms. Traditionally, LH was primarily associated with its role in triggering ovulation and supporting the corpus luteum. Accumulating evidence, however, suggests that LH also influences follicular steroidogenesis, oocyte maturation and endometrial receptivity. Despite these insights, the role of LH in ovarian stimulation remains under debate, particularly outside of patients with hypogonadotropic hypogonadism, characterized by hypothalamic amenorrhoea. Notably, recent molecular and clinical evidence supports the benefits of including LH activity in ovarian stimulation protocols for select patient groups. LH activity can be derived from human menopausal gonadotrophin, which contains both FSH and LH activity, with LH primarily driven by HCG; recombinant LH (rLH), or recombinant FSH + LH (rFSH + rLH). This review clarifies the evolving role of LH activity in ART, bridging foundational biological insights with the emerging paradigm of patient-specific treatment strategies to optimize reproductive outcomes.
Value-based outcome measures for ART: much room for improvement
No consensus exists on the preferred way to represent the outcomes of assisted reproductive technology (ART). Currently used outcomes are usually procedure driven and generated by healthcare professionals. Value-based healthcare, emphasizing the need to define preferred outcomes with and around patients, has raised much attention in medicine outside fertility care. This commentary outlines how currently used outcome measures could detrimentally affect the way ART is practised, and proposes ways to improve such outcomes.
Lifetime fiscal impact of IVF-born singletons in Turkey: a female-age-stratified analysis
What is the fiscal impact of IVF-born singletons in Turkey stratified by maternal age group?
Mid-luteal serum progesterone concentrations in modified natural cycles for embryo transfer: a prospective blinded study
Does mid-luteal serum progesterone concentration influence pregnancy outcomes in modified natural cycle frozen embryo transfer (mNC-FET) with ovulation triggering and luteal phase support (LPS)?
Sexual intercourse and vaginal absorption of progesterone (SexVAP): a cross-over randomized prospective pilot study
Does use of male condoms during sexual intercourse affect serum progesterone levels in women taking hormonal replacement therapy (HRT) with vaginal progesterone, compared with unprotected sexual intercourse and sexual abstinence as the reference for progesterone absorption?
One-step warming technique for vitrified human blastocysts using commercially available thawing solutions
What are the re-expansion rates and clinical outcomes obtained when employing a one-step warming technique using three commercially available thawing solutions on vitrified blastocysts, and how do they compare with the standard multi-step warming technique?
To discard or not to discard 1PNs? A systematic review and meta-analysis on 291,474 embryos
Unlike embryos that display two pronuclei (2PN), monopronucleated (1PN) embryos are assumed to be haploid and can be routinely discarded. Although there are reports of live births after 1PN embryo transfer, the developmental and clinical prognosis of 1PN embryos has not been systematically evaluated. The aim of this review was to elucidate the developmental, clinical and neonatal outcomes of 1PN embryos compared with 2PN embryos. Twenty-four studies met the inclusion criteria. The blastulation rate was lower in 1PN embryos compared with 2PN embryos [risk ratio (RR) 0.50, 95% CI 0.48-0.51]. The live birth rate was lower in 1PN blastocysts when untested (RR 0.81, 95% CI 0.72-0.90), but was similar after euploidy confirmation by preimplantation genetic testing for aneuploidy (RR 0.85, 95% CI 0.59-1.23). The euploidy rate was comparable in 1PN and 2PN embryos (RR 0.91, 95% CI 0.81-1.02). In a subgroup analysis of untested embryos, 1PN-intracytoplasmic sperm injection (ICSI) blastocysts had a lower live birth rate compared with 2PN-ICSI blastocysts (RR 0.26, 95% CI 0.13-0.50), while no difference was observed with IVF (RR 0.93, 95% CI 0.82-1.06). These results are particularly important for patients with a poor prognosis and limited 2PN embryos, and can aid reproductive professionals to counsel patients on the clinical use of 1PN embryos. Future studies should utilise time-lapse and preimplantation genetic testing technologies for confirmation of diploidy and biparental inheritance. Monopronucleated embryos can be viable, expanding options beyond 2PN embryos.
Real-life experience with transvaginal radiofrequency ablation in infertile patients with types 2 and 3 fibroids
Transvaginal radiofrequency ablation (TRFA) may offer a safe and effective alternative to surgery for infertile women with type 2 or 3 fibroids under 4 cm diameter that compromise the uterine cavity.
Offering semen cryopreservation to transgender persons birth-assigned male: qualitative interviews on motivation and attitudes
What are the considerations and opinions of individuals assigned male at birth (AMAB) when offered fertility preservation in Denmark, where the preservation of gametes is reimbursed?
Association between endometriosis and endometrial polyps: a systematic review and meta-analysis
Endometriosis and endometrial polyps are oestrogen-dependent conditions that frequently co-occur, yet their combined prevalence remains unclear. This study synthesized data on the prevalence of endometrial polyps in women with endometriosis and vice versa. Systematic searches of PubMed, Embase and Scopus were conducted up to 1 October 2024. Observational studies reporting the prevalence of endometrial polyps in women with endometriosis, and vice versa, were included. Random-effects models calculated pooled proportions and risk ratios (RR) with 95% CI. Risk of bias was assessed using the Newcastle-Ottawa scale, and evidence/certainty was graded using the Grading of Recommendations Assessment, Development and Evaluation guidelines. The protocol was registered in PROSPERO (CRD42024595167). Twenty-two studies with 10,928 patients (8154 women with infertility) were included. Women with endometriosis (1757 patients) had a significantly higher risk of endometrial polyps (RR 2.18, 95% CI 1.58-3.00; I = 83.5%; P < 0.001), and women with polyps (2130 patients) had a significantly higher risk of endometriosis (RR 2.05, 95% CI 1.61-2.62; I = 82.5%; P < 0.001), compared with controls (5590 and 5217 patients, respectively). Subgroup analyses by infertility status and disease stage confirmed these findings. A gradient effect showed a significantly higher risk of endometrial polyps in women with stage III-IV endometriosis compared with women with stage I-II endometriosis (RR 1.19, 95% CI 1.08-1.32; I = 0.0%; P < 0.001). Endometriosis and endometrial polyps are strongly associated, particularly in women with infertility. Despite low-quality evidence, these findings emphasize the importance of better detection and targeted interventions to enhance fertility outcomes.
Peri-conceptional maternal vulnerability risk score and embryonic growth: the Rotterdam Periconception Cohort
What is the association of peri-conceptional maternal vulnerability, assessed through a weighted multi-domain risk score with embryonic growth?
Artificial intelligence-assisted selective modified natural frozen embryo transfer
Can an artificial intelligence algorithm assist in selectively triggering natural-cycle frozen embryo transfer (NC-FET) to avoid transfers on undesired days?
Is ovarian reserve associated with an increased risk of miscarriage? A systematic review and meta-analysis
This review determines the association between ovarian reserve markers, anti-Müllerian hormone (AMH) and antral follicle count (AFC), with risk of miscarriage in women undergoing assisted reproductive technology. A systematic search of PubMed, Embase, Cochrane Library and Google Scholar from inception to September 2023 identified 16 retrospective studies, including 43,147 patients. A meta-analysis using a random effects model demonstrated that low AMH concentration is associated with a significantly increased risk of miscarriage compared with medium and high AMH concentration (OR 1.48, 95% CI 1.20 to 1.83, P = 0.0002). When stratified by age, the risk remained significant in women aged younger than 35 years (OR 1.34, 95% CI 1.17 to 1.54, P < 0.0001); however, results were not significant among women aged 35 years or younger (OR 1.29, 95% CI 0.95 to 1.76, P = 0.10). Similarly, low AFC was associated with an increased risk of miscarriage across all ages (OR 1.80, 95% CI 1.33 to 2.45, P = 0.0002). After age adjustment, the association was significant in women aged younger than 35 years (OR 1.61, 95% CI 1.20 to 2.16, P = 0.002), but not among women aged 35 years or older (OR 1.41, 95% CI 0.90 to 2.22, P = 0.14). Therefore, a reduced ovarian reserve is associated with an increased risk of miscarriage, although results are only significant among women aged younger than 35 years.
The role of seminal oxidation-reduction potential in male infertility: systematic review and meta-analysis
This systematic review/meta-analysis was conducted using MEDLINE, CENTRAL, Embase and randomized controlled trial registries up to December 2024. The study evaluated whether seminal oxidation-reduction potential (ORP), as a marker of oxidative stress, differs between fertile men and men with infertility, and whether it is associated with semen quality. Thirteen studies were included in the meta-analysis, showing lower ORP levels in fertile men compared with men with infertility [(weighted mean difference (WMD) -4.07, 95% CI -5.80 to -2.35], and in patients with normal semen parameters compared with patients with at least one abnormal semen parameter (WMD -2.39, 95% CI -4.01 to -0.76). Patients with high ORP levels had a lower sperm concentration (WMD -35.76, 95% CI -52.40 to -19.11), total sperm count (WMD -126.41, 95% CI -208.59 to -44.22), total motility (WMD -8.80, 95% CI -11.17 to -6.44), progressive motility (WMD -7.62, 95% CI -10.74 to -4.49) and percentage of normal morphology (WMD -1.55, 95% CI -1.93 to -1.16); and a higher proportion of immotile spermatozoa (WMD +8.46, 95% CI +1.67 to +15.26) compared with patients with low ORP levels. In conclusion, seminal ORP levels are negatively associated with male fertility, sperm concentration, total sperm count, total and progressive motility, and normal morphology; and positively associated with immotile spermatozoa.
