Reproductive outcomes and reproductive health care utilization among male survivors of childhood cancer: A DCCSS-LATER study.

BACKGROUND: Treatment-related gonadal dysfunction leading to fertility problems is a frequently encountered late effect in childhood cancer survivors (CCSs). This study evaluated reproductive outcomes and reproductive health care utilization among male CCSs compared with male siblings. METHODS: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor LATER study part 1, a questionnaire and linkage study. A questionnaire addressing reproductive outcomes and reproductive health care was completed by 1317 male CCSs and 407 male siblings. A total of 491 CCSs and 185 siblings had a previous or current desire for children and were included in this study. RESULTS: Fewer CCSs had biological children compared with siblings (65% vs. 88%; p < .001). The type of conception by men who fathered a child was comparable between CCSs and siblings (spontaneous conception of 90% of both groups; p = .86). The percentage of men who had consulted a reproductive specialist because of not siring a pregnancy was higher in CCSs compared with siblings (34% vs. 12%; p < .001). Following consultation, fewer CCSs underwent assisted reproductive techniques (ART) compared with siblings (41% vs. 77%; p = .001). After ART, fewer CCSs fathered a child compared with siblings (49% vs. 94%; p = .001). CONCLUSIONS: More male survivors consult a reproductive specialist, but fewer survivors undergo ART and father a child after ART compared with siblings. This insight is important for understanding potential problems faced by survivors regarding family planning and emphasizes the importance of collaboration between oncologists and reproductive specialists.

Economic evaluations of assisted reproductive technologies in high-income countries: a systematic review.

STUDY QUESTION: Which assited reproductive technology (ART) interventions in high-income countries are cost-effective and which are not? SUMMARY ANSWER: Among all ART interventions assessed in economic evaluations, most high-cost interventions, including preimplantation genetic testing for aneuploidy (PGT-A) for a general population and ICSI for unexplained infertility, are unlikely to be cost-effective owing to minimal or no increase in effectiveness. WHAT IS KNOWN ALREADY: Approaches to reduce costs in order to increase access have been identified as a research priority for future infertility research. There has been an increasing number of ART interventions implemented in routine clinical practice globally, before robust assessments of evidence on economic evaluations. The extent of clinical effectiveness of some studied comparisons has been evaluated in high-quality research, allowing more informative decision making around cost-effectiveness. STUDY DESIGN, SIZE, DURATION: We performed a systematic review and searched seven databases (MEDLINE, PUBMED, EMBASE, COCHRANE, ECONLIT, SCOPUS, and CINAHL) for studies examining ART interventions for infertility together with an economic evaluation component (cost-effectiveness, cost-benefit, cost-utility, or cost-minimization assessment), in high-income countries, published since January 2011. The last search was 22 June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two independent reviewers assessed publications and included those fulfilling the eligibility criteria. Studies were examined to assess the cost-effectiveness of the studied intervention, as well as the reporting quality of the study. The chosen outcome measure and payer perspective were also noted. Completeness of reporting was assessed against the Consolidated Health Economic Evaluation Reporting Standard. Results are presented and summarized based on the intervention studied. MAIN RESULTS AND THE ROLE OF CHANCE: The review included 40 studies which were conducted in 11 high-income countries. Most studies (n = 34) included a cost-effectiveness analysis. ART interventions included medication or strategies for controlled ovarian stimulation (n = 15), IVF (n = 9), PGT-A (n = 7), single embryo transfer (n = 5), ICSI (n = 3), and freeze-all embryo transfer (n = 1). Live birth was the mostly commonly reported primary outcome (n = 27), and quality-adjusted life years was reported in three studies. The health funder perspective was used in 85% (n = 34) of studies. None of the included studies measured patient preference for treatment. It remains uncertain whether PGT-A improves pregnancy rates compared to IVF cycles managed without PGT-A, and therefore cost-effectiveness could not be demonstrated for this intervention. Similarly, ICSI in non-male factor infertility appears not to be clinically effective compared to standard fertilization in an IVF cycle and is therefore not cost-effective. Interventions such as use of biosimilars or HMG for ovarian stimulation are cheaper but compromise clinical effectiveness. LIMITATIONS, REASONS FOR CAUTION: Lack of both preference-based and standardized outcomes limits the comparability of results across studies. The selection of efficacy evidence offered for some interventions for economic evaluations is not always based on high-quality randomized trials and systematic reviews. In addition, there is insufficient knowledge of the willingness to pay thresholds of individuals and state funders for treatment of infertility. There is variable quality of reporting scores, which might increase uncertainty around the cost-effectiveness results. WIDER IMPLICATIONS OF THE FINDINGS: Investment in strategies to help infertile people who utilize ART is justifiable at both personal and population levels. This systematic review may assist ART funders decide how to best invest to maximize the likelihood of delivery of a healthy child. STUDY FUNDING/COMPETING INTEREST(S): There was no funding for this study. E.C. and R.W. receive salary support from the National Health and Medical Research Council (NHMRC) through their fellowship scheme (EC GNT1159536, RW 2021/GNT2009767). M.D.-T. reports consulting fees from King Fahad Medical School. All other authors have no competing interests to declare. REGISTRATION NUMBER: Prospero CRD42021261537.

Differences in medically assisted reproduction use by sexual identity and partnership: a prospective cohort of cisgender women.

STUDY QUESTION: Does medically assisted reproduction (MAR) use among cisgender women differ among those with same-sex partners or lesbian/bisexual identities compared to peers with different-sex partners or heterosexual identities? SUMMARY ANSWER: Women with same-sex partners or lesbian/bisexual identities are more likely to utilize any MAR but are no more likely to use ART (i.e. IVF, reciprocal IVF, embryo transfer, unspecified ART, ICSI, and gamete or zygote intrafallopian transfer) compared to non-ART MAR (i.e. IUI, ovulation induction, and intravaginal or intracervical insemination) than their different-sex partnered and completely heterosexual peers. WHAT IS KNOWN ALREADY: Sexual minority women (SMW) form families in myriad ways, including through fostering, adoption, genetic, and/or biological routes. Emerging evidence suggests this population increasingly wants to form genetic and/or biological families, yet little is known about their family formation processes and conception needs. STUDY DESIGN, SIZE, DURATION: The Growing Up Today Study is a US-based prospective cohort (n = 27 805). Participants were 9-17 years of age at enrollment (1996 and 2004). Biennial follow-up is ongoing, with data collected through 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cisgender women who met the following criteria were included in this sample: endorsed ever being pregnant; attempted a pregnancy in 2019 or 2021; and endorsed either a male- or female-sex partner OR responded to questions regarding their sexual identity during their conception window. The main outcome was any MAR use including ART (i.e. procedures involving micromanipulation of gametes) and non-ART MAR (i.e. nonmanipulation of gametes). Secondary outcomes included specific MAR procedures, time to conception, and trends across time. We assessed differences in any MAR use using weighted modified Poisson generalized estimating equations. MAIN RESULTS AND THE ROLE OF CHANCE: Among 3519 participants, there were 6935 pregnancies/pregnancy attempts and 19.4% involved MAR. A total of 47 pregnancies or pregnancy attempts were among the same-sex partnered participants, while 91 were among bisexual participants and 37 among lesbian participants. Participants with same-sex, compared to different-sex partners were almost five times as likely to use MAR (risk ratio [95% CI]: 4.78 [4.06, 5.61]). Compared to completely heterosexual participants, there was greater MAR use among lesbian (4.00 [3.10, 5.16]) and bisexual (2.22 [1.60, 3.07]) participants compared to no MAR use; mostly heterosexual participants were also more likely to use ART (1.42 [1.11, 1.82]) compared to non-ART MAR. Among first pregnancies conceived using MAR, conception pathways differed by partnership and sexual identity groups; differences were largest for IUI, intravaginal insemination, and timed intercourse with ovulation induction. From 2002 to 2021, MAR use increased proportionally to total pregnancies/pregnancy attempts; ART use was increasingly common in later years among same-sex partnered and lesbian participants. LIMITATIONS, REASONS FOR CAUTION: Our results are limited by the small number of SMW, the homogenous sample of mostly White, educated participants, the potential misclassification of MAR use when creating conception pathways unique to SMW, and the questionnaire's skip logic, which excluded certain participants from receiving MAR questions. WIDER IMPLICATIONS OF THE FINDINGS: Previous studies on SMW family formation have primarily focused on clinical outcomes from ART procedures and perinatal outcomes by conception method, and have been almost exclusively limited to European, clinical samples that relied on partnership data only. Despite the small sample of SMW within a nonrepresentative study, this is the first study to our knowledge to use a nonclinical sample of cisgender women from across the USA to elucidate family formation pathways by partnership as well as sexual identity, including pathways that may be unique to SMW. This was made possible by our innovative approach to MAR categorization within a large, prospective dataset that collected detailed sexual orientation data. Specifically, lesbian, bisexual, and same-sex partnered participants used both ART and non-ART MAR at similar frequencies compared to heterosexual and different-sex partnered participants. This may signal differential access to conception pathways owing to structural barriers, emerging conception trends as family formation among SMW has increased, and a need for conception support beyond specialized providers and fertility clinics. STUDY FUNDING/COMPETING INTEREST(S): The research reported in this publication was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health (NIH), under award number R01MD015256. Additionally, KRSS is supported by NCI grant T32CA009001, AKH by the NCI T32CA057711, PC by the NHLBI T32HL098048, BM by the Stanford Maternal Child Health Research Institute Clinical Trainee Support Grant and the Diversity Fellowship from the American Society for Reproductive Medicine Research Institute, BGE by NICHD R01HD091405, and SM by the Thomas O. Pyle Fellowship through the Harvard Pilgrim Health Care Foundation and Harvard University, NHLBI T32HL098048, NIMH R01MH112384, and the William T. Grant Foundation grant number 187958. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The first author recently had a leadership role in the not-for-profit program, The Lesbian Health Fund, a research fund focused on improving the health and wellbeing of LGBTQ+ women and girls. The fund did not have any role in this study and the author's relationship with the fund did not bias the findings of this manuscript. TRIAL REGISTRATION NUMBER: N/A.

Effects of SARS-CoV-2 infection during ovarian stimulation on ART outcomes.

RESEARCH QUESTION: Does severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during ovarian stimulation affect assisted reproductive technology outcomes? DESIGN: This retrospective cohort study conducted at the Reproductive Medicine Centre of The First Affiliated Hospital of Anhui Medical University aimed to assess the effects of acute SARS-CoV-2 infection during IVF on treatment outcomes and the reproductive system. The study included 151 treatment cycles involving couples with coronavirus disease 2019 (COVID-19) during ovarian stimulation, along with 224 cycles of non-infected couples as a control group. Clinical characteristics and laboratory parameters were analysed, including total gonadotrophin dosage, duration of ovarian stimulation, number of oocytes retrieved, fertilization method, fertilization rate, and number of blastocyst embryos available. Forty-six follicular fluid samples, 38 semen samples and 78 embryo culture medium samples from patients with COVID-19 were tested for SARS-CoV-2 RNA using reverse transcription polymerase chain reaction assay. RESULTS: The treatment and control groups showed similar cycle characteristics, including fertilization method, total gonadotrophin dosage and duration of ovarian stimulation. The mean number of oocytes retrieved per cycle and rate of mature oocytes in intracytoplasmic sperm injection cycles were comparable. No significant difference was observed in the total number of blastocyst embryos available between the groups. Furthermore, no SARS-CoV-2 RNA was detected in any of the samples of patients with COVID-19. CONCLUSIONS: In conclusion, acute SARS-CoV-2 infection during ovarian stimulation does not have a significant impact on IVF treatment outcomes. Additionally, no risk to the reproductive system was observed in patients infected with SARS-CoV-2. Therefore, individuals with asymptomatic or mild COVID-19 can safely continue IVF treatment. Future research is needed to investigate the long-term effects of COVID-19 on fertility and reproductive outcomes.

Sperm DNA fragmentation and infertility: a narrative review.

PURPOSE: The purpose of this narrative review is to provide a practical understanding of sperm DNA fragmentation (SDF) in the management of male infertility. METHODS: A search for systematic reviews and meta-analyses (SRMA) on SDF between April 1st, 2018 and April 1st, 2023 was performed using PubMed and articles were selected as per their relevance to the topic. Guidelines from major societies were also reviewed. Three clinical cases are reported and discussed. RESULTS: The search initially identified 80 articles. We selected 13 SRMAs based on their relevance to the topic. Of the 13 SRMAs, 7 evaluated the effect of SDF on assisted reproductive technology (ART) outcomes and recurrent pregnancy loss, 3 studied the effect of varicocele repair on SDF, and 3 evaluated the role of SDF involving lifestyle and environmental health factors including body mass index and male factor treatment strategies. CONCLUSION: Evidence suggests that increased SDF has a negative impact on natural pregnancy and ART outcomes. SDF testing may be particularly important in the infertility evaluation of men with varicoceles, idiopathic or unexplained infertility, recurrent pregnancy loss, or previous ART failure. Further studies are needed on SDF testing and the implications it can have on male factor infertility and pregnancy outcomes as well as its implementation in the setting of ART.

Live birth rate after oocyte donation in females diagnosed with turner syndrome: a systematic review and meta-analysis.

BACKGROUND: An enduring challenge for women diagnosed with Turner syndrome (TS) is infertility. Oocyte donation (OD) offers a chance of pregnancy for these patients. However, current data on pregnancy outcomes are inadequate. Hence, this systematic review aims to explore the clinical outcomes of OD in patients with TS. METHODS: A systematic search was conducted in PubMed, Web of Sciences, Scopus, and Embase for relevant papers from 1 January 1990 to 30 November 2023. Our primary research objective is to determine the live birth rate among women with TS who have undergone in vitro fertilization (IVF) using OD for fertility purposes. Specifically, we aim to calculate the pooled live birth rates per patient and per embryo transfer (ET) cycle. For secondary outcomes, we have analyzed the rates of clinical pregnancy achievement per ET cycle and the incidence of gestational hypertensive complications per clinical pregnancy. Prevalence meta-analyses were performed using STATA 18.0 by utilizing a random-effects model and calculating the pooled rates of each outcome using a 95% confidence interval (CI). RESULTS: A total of 14 studies encompassing 417 patients were systematically reviewed. Except for one prospective clinical trial and one prospective cohort study, all other 12 studies had a retrospective cohort design. Our meta-analysis has yielded a pooled live birth rate per patient of 40% (95% CI: 29-51%; 14 studies included) and a pooled live birth rate per ET cycle of 17% (95% CI: 13-20%; 13 studies included). Also, the pooled clinical pregnancy achievement rate per ET cycle was estimated at 31% (95% CI: 25-36%; 12 studies included). Moreover, the pooled rate of pregnancy-induced hypertensive disorders per clinical pregnancy was estimated at 12% (95% CI: 1-31%; 8 studies included). No publication bias was found across all analyses. CONCLUSIONS: This study demonstrated promising pregnancy outcomes for OD in patients with TS. Further studies are essential to address not only the preferred techniques, but also the psychological, ethical, and societal implications of these complex procedures for these vulnerable populations. TRIAL REGISTRATION: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration code CRD42023494273.

Pregnancy and assisted reproductive technology use in Australian female transfusion-dependent haemoglobinopathy patients: a 20-year retrospective analysis.

BACKGROUND: In the last few decades, the life expectancy of patients with transfusion-dependent thalassaemia (TDT) and sickle cell disease (SCD) has improved significantly, in part because of improved iron chelation. Fertility challenges and pregnancy complications have historically limited reproductive options in this group; however, improved multi-disciplinary care has made infertility a chronic disease complication requiring attention. Despite this, there are very few reports and no Australian data describing fertility and pregnancy outcomes in this population. AIMS: To identify the rate of assisted reproductive technologies (ART) utilisation in our female transfusion-dependent haemoglobinopathy patients and to establish the nature of maternal and neonatal complications in this cohort. METHODS: A 20-year retrospective analysis (1997-2017) at an Australian centre captured data on conception rates, use of assisted reproductive techniques (ART), and pregnancy and neonatal outcomes in female transfusion-dependent haemoglobinopathy patients. RESULTS: Conception was attempted in 14 women (11 TDT and three SCD) during the study period. A total of 28 pregnancies resulting in 25 live births were recorded. ART supported 13 conceptions. A positive association was not identified between elevated mean serum ferritin and ART use; however, all patients with an established diagnosis of hypogonadotropic hypogonadism (HH) required ART. Maternal complications included gestational diabetes mellitus and post-partum haemorrhage. There were no cardiac complications. Two-thirds of women underwent lower segment caesarean section, with prematurity complicating 20% of births. There were no neonatal or maternal deaths. CONCLUSION: Pregnancy is an achievable goal for women with transfusion-dependent haemoglobinopathies, although the support of ART may be required in a subset of patients.

Assisted reproductive technologies could be associated with higher risk of parenting difficulties in women with postpartum major depression.

No increased risk of postpartum major depression (PPMD) was reported in women conceiving through assisted reproductive technologies (ART). However, ART may be associated with a higher risk of parenting difficulties in women with PPMD. In 359 women with a PPMD admitted to a Mother-Baby Unit (MBU), ART-women (4.2%) showed a 5-fold higher rate of parenting difficulties than those with spontaneous pregnancy (73.33% vs. 35.17%, multivariate ORa = 5.09 [1.48-17.48] p = 0.01). Specific support for mother-child relationship should be implemented in ART-women with PPMD.

Access to assisted human reproduction techniques in Colombia: Disparity between the recognition of reproductive rights and their effective implementation.

Public funding of assisted reproduction technologies (ARTs) is a controversial issue. Some health systems have proposed public funding of ARTs. In recent years, there has been evidence of a change in the line of jurisprudence and legislation in Colombia about this topic. This article analyzes the tension between the recognition of individual sexual and reproductive rights and the common good, in terms of the sustainability of the health system and the reasonable use of limited resources to meet the health needs of the population. This article concludes that, despite regulatory progress, there has been a lack of corresponding progress in their effective implementation and the recognition of reproductive rights.

Pregnancy in women with mitochondrial disease-A literature review and suggested guidance for preconception and pregnancy care.

Mitochondrial donation to reduce the risk of primary mitochondrial disease transmission from mother to child is now permitted under Australian law as part of a clinical trial. The energy demands of pregnancy have the potential to worsen mitochondrial disease symptoms and severity in affected women. We conducted a systematic literature review on mitochondrial disease in pregnancy; five cohort studies and 19 case reports were included. For many women with mitochondrial disease, pregnancy does not have a negative effect on health status. However, serious adverse outcomes may occur. We provide suggested guidelines for preconception counselling and antenatal care.

Follicular Fluid-Derived Extracellular Vesicles Influence on In Vitro Maturation of Equine Oocyte: Impact on Cumulus Cell Viability, Expansion and Transcriptome.

Cumulus cell (CC) expansion is pivotal for oocyte maturation, during which CCs release factors that initiate paracrine signaling within the follicular fluid (FF). The FF is abundant in extracellular vesicles (EVs) that facilitate intercellular communication. Although bovine and murine EVs can control cumulus expansion, these effects have not been observed in equines. This study aimed to assess the impact of FF-derived EVs (ffEVs) on equine CC expansion, viability, and transcriptome. Cumulus-oocyte complexes (COCs) that underwent in vitro maturation (IVM) in the presence (200 µg protein/mL) or absence (control) of ffEVs were assessed for cumulus expansion and viability. CCs were isolated after 12 h of IVM, followed by RNA extraction, cDNA library generation, and subsequent transcriptome analysis using next-generation sequencing. Confocal microscopy images illustrated the internalization of labeled ffEVs by CCs. Supplementation with ffEVs significantly enhanced cumulus expansion in both compacted (Cp, p < 0.0001) and expanded (Ex, p < 0.05) COCs, while viability increased in Cp groups (p < 0.01), but decreased in Ex groups (p < 0.05), compared to the controls. Although transcriptome analysis revealed a subtle effect on CC RNA profiles, differentially expressed genes encompassed processes (e.g., MAPK and Wnt signaling) potentially crucial for cumulus properties and, consequently, oocyte maturation.

From pathophysiology to practice: addressing oxidative stress and sperm DNA fragmentation in Varicocele-affected subfertile men.

Varicocele can reduce male fertility potential through various oxidative stress mechanisms. Excessive production of reactive oxygen species may overwhelm the sperm's defenses against oxidative stress, damaging the sperm chromatin. Sperm DNA fragmentation, in the form of DNA strand breaks, is recognized as a consequence of the oxidative stress cascade and is commonly found in the ejaculates of men with varicocele and fertility issues. This paper reviews the current knowledge regarding the association between varicocele, oxidative stress, sperm DNA fragmentation, and male infertility, and examines the role of varicocele repair in alleviating oxidative-sperm DNA fragmentation in these patients. Additionally, we highlight areas for further research to address knowledge gaps relevant to clinical practice.

Comparative cross-sectional study on sexual function of couples during pregnancy: Assisted reproductive techniques versus spontaneous conceptions.

This study aims to compare the sexual functions of couples undergoing assisted reproductive techniques (ART) with those conceiving spontaneously during pregnancy. A total of 102 couples participated in this cross-sectional study, with 68 couples in the spontaneous conception group and 34 couples in the ART group. Data collection was conducted face-to-face in the antenatal clinic using separate "Descriptive Information Form" for women and men, "Female Sexual Function Index (FSFI)" for women, and "Libido Scoring System (LSS)" for men. Descriptive statistical methods, Chi-square and Fisher exact tests, t-test, and Pearson correlation test were used for data analysis. It was observed that the mean FSFI total scores of women who conceived spontaneously and through ART during pregnancy were at a good level (≥30), while the mean LSS scores of their partners were at a moderate level (5-7). No statistically significant distinction existed among the groups. Further research is advisable by adjusting the sample selection criteria, such as gravida, duration of ART treatment, and gestational age.

Cette étude vise à comparer les fonctions sexuelles des couples soumis à des techniques de procréation assistée (ART) avec ceux qui conçoivent spontanément pendant la grossesse. Au total, 102 couples ont participé à cette étude transversale, dont 68 couples dans le groupe conception spontanée et 34 couples dans le groupe ART. La collecte de données a été réalisée en face-à-face dans la clinique prénatale en utilisant un « formulaire d'informations descriptives ¼ distinct pour les femmes et les hommes, un « indice de fonction sexuelle féminine (FSFI) ¼ pour les femmes et un « système de notation de la libido (LSS) ¼ pour les hommes. Des méthodes statistiques descriptives, les tests exacts du chi carré et de Fisher, le test t et le test de corrélation de Pearson ont été utilisés pour l'analyse des données. Il a été observé que les scores totaux moyens FSFI des femmes ayant conçu spontanément et par TAR pendant la grossesse étaient à un bon niveau (≥30), tandis que les scores moyens LSS de leurs partenaires étaient à un niveau modéré (5-7). Aucune distinction statistiquement significative n'existait entre les groupes. Des recherches plus approfondies sont recommandées en ajustant les critères de sélection des échantillons, tels que la gravité, la durée du traitement ART et l'âge gestationnel.

Analysis of the relationship between religion, abortion, and assisted reproductive technology: Insights into cross-national public opinion.

With advancement in reproductive technologies, public opinion regarding these procedures varies considerably across the world. While prominent public debates have focused on abortion, we know less about the factors shaping feelings regarding Assisted Reproductive Technologies (ART). Both procedures challenge the idea that human life starts with conception - with the fertilization of an embryo. Using European Values Survey data and multilevel modeling, we compare how religion and other personal and country-level factors shape disapproval toward abortion and ART. Conservative Protestants and people who are more engaged with their religion and live in a more religious country are more likely to disapprove of abortion and ART. More supportive polices and attitudes regarding ART, but not abortion, are correlated. Additionally, economic development moderates the relationship between personal religiosity and abortion, but not ART. This finding provides important insight into why abortion has remained such a controversial issue, even in richer nations.

Evolution of intracytoplasmic sperm injection: From initial challenges to wider applications.

Background: In vitro fertilization (IVF) has revolutionized infertility treatment. Nevertheless, male infertility requires more effective solutions. In 1992, the first-ever case of human birth via intracytoplasmic sperm injection (ICSI) was reported. ICSI involves microscopically injecting a sperm into an ovum. Successful ICSI has become a reliable therapy for couples facing infertility, a significant milestone. However, it has also introduced various challenges. This study also delves into ethical dilemmas arising from widespread ICSI use. Methods: This review traces the history of ICSI, presenting pioneering attempts, first successful attempts, and critical reports on account of the initial skepticism toward the technology. The review also focuses on chronological progress until ICSI was recognized as effective and became widely applied. Main findings: The review reveals that ICSI, although transformative, presents challenges. Successes include addressing male infertility and aiding fertilization. However, concerns arise regarding optimal sperm and embryo selection, genetic mutations, and long-term health implications. Ethical considerations surrounding ICSI's broad applications also surface. Conclusions: Despite its success and effectiveness, ICSI is still evolving as a therapeutic method. By comprehensively evaluating the historical progress and the current status of ICSI and exploring its future prospects, this study highlights the importance of ICSI in infertility treatment.

Efficacy and safety of follitropin delta versus follitropin alpha/beta in infertility treatment: A systematic review and meta-analysis.

Background: Follitropin δ may be an alternative to conventional follitropin α/ß for controlled ovarian stimulation (COS) within assisted reproductive treatment (ART), but its efficacy and safety remain unknown. We performed a random-effects meta-analysis to compare the efficacy and safety of follitropin δ and follitropin α/ß. Methods: We searched randomized controlled trials comparing follitropin δ and follitropin α/ß using MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and WHO-ITCRP on December 14, 2022. The primary outcomes were the live birth rate and the incidence of moderate or severe ovarian hyperstimulation syndrome (OHSS). The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation approach. The protocol was registered on the Open Science Framework. Results: Three studies involving 2682 participants were included in our meta-analysis. The results indicated that follitropin δ may result in little to no difference in live birth rates (risk ratio [RR], 1.12; 95% confidence interval [CI], 0.91-1.38; low certainty) and the incidence of moderate or severe OHSS (RR, 0.78; 95% CI, 0.48-1.26; low certainty) compared with follitropin α/ß. Conclusion: Follitropin δ may result in little to no difference in COS compared with follitropin α/ß, especially in terms of live births and safety.

Infertility in patients with uterine fibroids: a debate about the hypothetical mechanisms.

Fibroids are benign tumours of the myometrium and are the most common gynaecologic abnormality. Although most fibroids are asymptomatic, they can cause symptoms like heavy menstrual bleeding, pelvic pain, sexual dysfunction, pressure complaints, and infertility. The association between fibroids and infertility has been debated for decades. It is generally acknowledged that the closer the fibroid is to the uterine cavity and the endometrium lining, the more unfavourable effect it might have on fertility, reducing the odds for successful implantation and gestation. Based on the limited available literature, we propose and discuss seven hypotheses on the underlying mechanism by which fibroids may reduce fertility. (i) Fibroids can cause sexual dysfunction, as fibroids can cause dyspareunia, pelvic pain, and prolonged and heavy menstrual bleeding, which could interfere with sexual arousal and as a consequence the frequency of intercourse, resulting in a reduced probability of conception. (ii) Mechanical compression by fibroids on theinterstitial part of the fallopian tubes or deformation of uterine cavity could disturb oocyte and sperm transport. (iii) Fibroids can disturb peristalsis of the junctional zone in the myometrium, which could negatively influence oocyte and sperm transport as well as implantation. In addition, fibroids could induce a detrimental environment for implantation in other ways, by: (iv) changing the vagino-uterine microbiome; (v) disturbing the levels of inflammation and autophagy; (vi) inducing molecular changes in the endometrium; and (vii) inducing aberrant angiogenesis and altering the endometrial blood supply. After the discussion of these hypotheses, the implication of the influence of fibroids on early pregnancy loss is discussed. Surgical fibroid treatment is not tailored nor focussed on the pathophysiology of the fibroid; consequently it may be accompanied by recurrence of fibroids and risks of complications. Unravelling the pathogenic mechanisms about how fibroids influence fertility is essential to evolve classic surgical fibroid treatment. Instead of treatment of fibroid-related symptoms, the research should supports development of fibroid-targeted (pharmaceutical) treatment that is compatible with an active wish to become pregnant.

Association between serum AMH levels and IVF/ICSI outcomes in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

CONTEXT: Anti-Müllerian hormone (AMH) levels are increased in polycystic ovary syndrome (PCOS) patients and are associated with PCOS severity. OBJECTIVE: To evaluate the associations between serum AMH levels and in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) outcomes in patients with PCOS. DATA SOURCES: PubMed, Embase, and the Cochrane Library were searched on 11 July 2022. STUDY SELECTION: Studies reporting the association between serum AMH levels and IVF/ICSI outcomes in PCOS patients were considered for inclusion. The primary outcomes were clinical pregnancy, live birth, and ovarian hyperstimulation syndrome. DATA EXTRACTION: Data were extracted using a standardized data extraction form. Study quality was assessed independently by two groups of researchers. DATA SYNTHESIS: Nineteen studies were included in this review. Meta-analyses demonstrated that PCOS patients with a serum AMH level within the 75-100th percentile had a decreased odds of clinical pregnancy (OR: 0.77, 95% CI: 0.63-0.93) and livebirth (OR: 0.71; 95% CI: 0.58-0.87) compared to those within the 0-25th percentile. An increased AMH level was also correlated with an increased number of oocytes retrieved (SMD: 0.90, 95% CI: 0.30-1.51) and a lower odds of fertilization (OR: 0.92, 95% CI: 0.87-0.98). There was no significant difference in the number of MII oocytes (SMD: 1.85, 95% CI: -1.07-4.78), E2 on the day of hCG (SMD: 0.12; 95% CI: -0.98-1.23), or implantation (OR: 0.82, 95% CI: 0.28-2.39) between the two groups. In addition, we found significant dose-response associations between serum AMH level and clinical pregnancy, live birth, number of oocytes retrieved, and fertilization in PCOS patients. CONCLUSION: AMH may have clinical utility in counseling regarding IVF/ICSI outcomes among women with PCOS who wish to undergo fertility treatment. More large-scale, high-quality cohort studies are needed to confirm these findings.

Presentation, medical complications and development of gestational trophoblastic neoplasia of hydatidiform mole after intracytoplasmic sperm injection as compared to hydatidiform mole after spontaneous conception - a retrospective cohort study and literature review.

OBJECTIVE: To describe the natural history of hydatidiform mole (HM) after intracytoplasmic sperm injection (ICSI), emphasizing the clinical and oncological outcomes, as compared to patients who had HM after spontaneous conception (SC). STUDY DESIGN: Retrospective historical cohort study of patients with HM followed at the Rio de Janeiro Federal University, from January 1st 2000-December 31st 2020. RESULTS: Comparing singleton HM after SC to those following ICSI there were differences in terms of maternal age (24 vs 34 years, p < 0.01), gestational age at diagnosis (10 vs 7 weeks, p < 0.01), preevacuation human chorionic gonadotropin levels (200,000 vs 99,000 IU/L, p < 0.01), occurrence of genital bleeding (60.5 vs 26.9%, p < 0.01) and hyperemesis (23 vs 3.9%, p = 0.02) at presentation, and time to remission (12 vs 5 weeks, p < 0.01), respectively. There were no differences observed in the cases of twin mole, regardless of the form of fertilization that gave rise to HM, except molar histology with greater occurrence of partial hydatidiform mole (10.7 vs 40.0%, p = 0.01) following ICSI. Univariate logistic regression for occurrence of postmolar GTN after ICSI identified no predictor variable for this outcome. However, after adjusting for maternal age and complete hydatidiform mole histology, multivariable logistic regression showed the risk of GTN with HM after ICSI had an adjusted odds ratio of 0.22 (95%CI:0.05-0.93, p = 0.04), suggesting a possible protective effect when compared to HM after SC. CONCLUSIONS: Singleton HM after ICSI are diagnosed earlier in gestation, present with fewer medical complications, and may be less likely to develop GTN when compared with HM after SC.

Incidence of and indications for sperm donor restriction - analysis of patients continuing treatment: a retrospective single-centre study.

RESEARCH QUESTION: What are the incidence of and indications for sperm donor restriction due to suspected/confirmed disease risk, and the future treatment choices of patients using these sperm donors? DESIGN: This single-centre retrospective study involved donors who had restrictions on the use of their imported spermatozoa from January 2010 to December 2019, and current or previous recipients. Indications for sperm restriction and the characteristics of patients undergoing medically assisted reproduction (MAR) treatment with these specimens at the time of restriction were collected. Differential characteristics of women who decided on whether or not to contintue the procedure were assessed. Characteristics potentially leading to treatment continuation were identified. RESULTS: Of 1124 sperm donors identified, 200 (17.8%) were restricted, most commonly for multifactorial (27.5%) and autosomal recessive (17.5%) disorders. The spermatozoa had been used for 798 recipients, of whom 172, receiving spermatozoa from 100 donors, were informed about the restriction and constituted the 'decision cohort'. The specimens from the restricted donors were accepted by 71 (approximately 40%) patients, with 45 (approximately 63%) eventually using the restricted donor for their future MAR treatment. The odds of accepting the restricted spermatozoa decreased with increasing age (OR 0.857, 95% CI 0.800-0.918, P < 0.001) and the time between MAR treatment and the restriction date (OR 0.806, 95% CI 0.713-0.911, P < 0.001). CONCLUSION: Donor restriction due to suspected/confirmed disease risk is relatively frequent. This affected a relevant number of women (around 800), of whom 172 (approximately 20%) had to decide whether or not to use these donors further. Although donor screening is being performed thoroughly, there remain health risks for donor children. Realistic counselling of all stakeholders involved is necessary.