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Endometriosis is one of the most common gynecologic conditions that women face throughout their lives. Despite advances in technology, diagnosis and treatment of this relapsing and remitting condition is still challenging for many women. This review focuses on literature pertaining to minimal/mild (stage I/II) endometriosis and its impact on fertility. The effectiveness of medical interventions to improve infertility and obstetric outcomes in both natural and assisted reproductive technologies cycles remains debated. The recent ESHRE guidelines suggests that operative laparoscopy could be considered for rASRM stage I/II endometriosis as it improves ongoing pregnancy rates.

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Purpose: Oncology clinicians are appropriately positioned to facilitate discussions of assisted reproductive technologies including preimplantation genetic testing for monogenic disease (PGT-M), in the context of cancer treatment or surveillance. Yet, reproductive services, including PGT-M, remain one of the least implemented services in oncology. No studies to date have explored which practice resources the clinicians need to increase knowledge of PGT-M. The objective of this study was to explore the specific needs of oncology clinicians to help maximize the reproductive potential of young adult patients with hereditary cancers. Methods: Participants were recruited through notices circulated on social media platforms and snowball sampling. Participants completed a brief online survey to confirm eligibility. Eligible participants completed a virtual, semi-structured interview. Interviews focused on clinician experiences with PGT-M and initiating referrals to fertility specialists. Thematic analysis was conducted using a constant comparative approach to identify current clinical practices. Results: This study found that PGT-M discussions are not necessarily within the scope of responsibilities for oncology clinicians owing to prioritization of cancer treatment and overall lack of knowledge. Participants need accessible resources and timely support for reproductive planning in the context of cancer treatment. Participants desire a streamlined referral pathway to professionals trained in oncofertility to help address their patient's reproductive needs. Conclusion: Our study identified that educational and referral resources to reproductive specialists are needed to maximize reproductive potential across the cancer continuum. These findings provide a foundation for larger studies that can inform standard-of-care recommendations in the emerging field of oncofertility.

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Key Clinical Message: To raise awareness about the increasing incidence of superfetation and heterotopic pregnancy in patients with ovarian induction, their insidious symptoms of abdominal pain, anemia, and hemodynamic instability in early pregnancy, and the usefulness of transvaginal ultrasound (TVUS) and quantitative beta human chorionic gonadotrophin (b-hCG) for diagnosis. Abstract: Superfetation, occurrence of ovulation, fertilization, and implantation during an ongoing pregnancy and heterotopic pregnancy (HP) simultaneous presence of intrauterine and extrauterine pregnancies are infrequent phenomena. We report a case where both coexisted, challenges in diagnosis and management and association with the widespread use of assisted reproductive technologies (ARTs). A 32-year-old woman, who previously underwent ovulation induction therapy, presented with abdominal pain at 8 weeks pregnancy according to her last menstrual period. The patient had high quantitative serum beta-human chorionic gonadotropin (b-hCG) (30,883 mIU/mL). She was vitally stable and not anemic. Transvaginal ultrasound (TVUS) revealed two pregnancies at different gestational ages: an intrauterine pregnancy at 5 weeks and 3 days, and a right intact tubal ectopic pregnancy at 10 weeks and 5 days. Superfetation resulting in HP was then diagnosed. Subsequently, the patient underwent right laparoscopic salpingectomy. The intrauterine pregnancy progressed normally, resulting in delivery of a healthy full-term neonate via Cesarean section at 38 weeks. Superfetation is typically rare from suppression of follicular development and ovulation during pregnancy. Various theories have been proposed to explain its etiology, including polyovulation, delayed blastocyst implantation, and abnormal estrogen and b-hCG surges. In superfetation, an embryo resulting from a previous conception coexists with another embryo, either intrauterine, resulting in diamniotic dizygotic twins with significantly different gestational ages, or extrauterine resulting in HP. Despite being particularly challenging to diagnose because its presenting symptoms can overlap with those of other more common clinical conditions in early pregnancy, HP is increasingly seen with ARTs. In addition, the treatment of HP is versatile, ranging from expectant management to laparoscopic surgery. High level of suspicion for HP and superfetation is crucial in patients who, after ART, present with abdominal pain, hemodynamic instability, or anemia. Additionally, patients planning to undergo subsequent ART cycles should be thoroughly screened with b-hCG and TVUS to exclude an ongoing intrauterine or extrauterine pregnancy.

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PURPOSE: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18-39 years) cancer. METHODS: This study included n = 1457 male and n = 2112 female long-term survivors (Mage = 43-45 years; 5-22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry. RESULTS: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2-3.6]), not having children (OR = 5.0; 95%CI [3.2-7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to "others"), and more intense treatments (OR = 1.5; 95%CI [1.1-2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. CONCLUSIONS: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors' well-being. IMPLICATIONS FOR CANCER SURVIVORS: The extent to which cryopreservation positively affects survivors' well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.

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Infertility is a condition defined by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse or due to an impairment of a person's capacity to reproduce either as an individual or with their partner. The authors have set out to succinctly investigate, explore, and assess infertility treatments, harnessing the potential of stem cells to effectively and safely treat infertility; in addition, this paper will present the legal and regulatory complexities at the heart of stem cell research, with an overview of the legislative state of affairs in six major European countries. For couples who cannot benefit from assisted reproductive technologies (ART) to treat their infertility, stem-cells-based approaches have been shown to be a highly promising approach. Nonetheless, lingering ethical and immunological uncertainties require more conclusive findings and data before such treatment avenues can become mainstream and be applied on a large scale. The isolation of human embryonic stem cells (ESCs) is ethically controversial, since their collection involves the destruction of human embryonic tissue. Overall, stem cell research has resulted in important new breakthroughs in the treatment of infertility. The effort to untangle the complex web of ethical and legal issues associated with such therapeutic approaches will have to rely on evidence-based, broadly shared standards, guidelines, and best practices to make sure that the procreative rights of patients can be effectively reconciled with the core values at the heart of medical ethics.

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Uterine fibroids significantly impact women's reproductive health, influencing fertility potential and pregnancy outcomes. Their growth, often facilitated by hormonal influences like estrogen and progesterone, can cause considerable disruptions in the uterus, leading to symptoms and complications that impact the quality of life and reproductive prospects of women.This article provides an exhaustive discussion of uterine fibroids, including pathophysiology, their impact on endometrial function, receptivity, fertility, and pregnancy outcomes, and the management of infertility in patients with uterine fibroids. It underlines the critical role of uterine fibroids in women's reproductive health, emphasizing the importance of effective diagnosis and treatment to promote fertility and improve pregnancy outcomes.

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Background: Over 8 million individuals worldwide have been conceived through assisted reproductive technologies (ART). There is conflicting evidence on the cardiovascular health of ART offspring. This study aimed to investigate vascular function in a cohort of children, adolescents and young adults conceived through ART compared to spontaneously conceived peers. Methods: Anthropometric variables, diet quality, level of physical activity and sedentary behavior were assessed. An extensive evaluation of vascular function was conducted. Blood pressure as well as endothelial function were evaluated. Carotid intima-media thickness was recorded sonographically. Blood draws were taken to determine blood lipids as well as HbA1c. Results: In total, 66 ART subjects conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection and 86 spontaneously conceived peers were included in this observational cohort study. Both groups were similar in age [11.31 (8.10-18.00) vs. 11.85 (8.72-18.27) years, P=0.373]. ART subjects displayed a significantly higher body fat percentage [19.30% (15.80-26.02%) vs. 15.91% (13.21-21.00%), P=0.007]. Both groups did not differ significantly in diet quality, physical activity, sedentary behavior, and vascular function. Blood lipids and HbA1c were comparable between both groups. ART subjects showed significantly lower levels of triglycerides compared to spontaneously conceived peers. The prevalence of lipoprotein (a) [Lp(a)] ≥50 mg/dL tended to be higher within the ART cohort. Vascular function did not deteriorate more profoundly with age in ART subjects than in spontaneously conceived peers. Conclusions: The results of the current study do not indicate a significantly lower vascular function in a cohort of children, adolescents and young adults conceived through ART compared to spontaneously conceived peers. Future studies should address the prevalence of elevated Lp(a) levels in infertile individuals who sought ART treatment. In addition, more studies evaluating body fat percentage as well as cardiovascular morbidity in adult ART subjects are required. For a more precise cardiovascular risk stratification, multi-center studies with larger ART sample sizes, preferably at adult age, are required in the future.

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Abstract: Law 40/2004, the Italian piece of legislation governing access to assisted reproductive technologies (ART), is relatively young, compared to the number of years that have passed since the first attempts at ART in the world. Still, such a law has undergone several revisions in recent years, mostly by court rulings, and such changes are indeed necessary in light of the constant evolution in ART innovations. Then, the COVID-19 pandemic struck on a global scale, disrupting virtually all aspects of social and economic life. COVID-19's impact on fertility has to do, although it is not limited to, the distribution and function of ACE2 in the female reproductive system: such receptors are in fact expressed extensively in the ovaries, uterus, vagina and placenta. We point out that overcoming the "demographic winter" Italy has been going through, compounded by the pandemic, will require major adjustments in the way we ensure access to ART services in an equitable, sustainable and affordable fashion for all who wish to fulfill their reproductive potential and have been prevented to do so by legal, regulatory and financial factors.

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INTRODUCTION: Despite the considerable progress made in assisted reproductive technologies (ART), the implantation rate of transferred embryos remains low and in many cases, the reasons for failure remain unclear. We aimed to determine the potential impact of female and male partners' reproductive tract microbiome composition on ART outcome. MATERIAL AND METHODS: The ART couples (n = 97) and healthy couples (n = 12) were recruited into the study. The smaller healthy group underwent a careful selection according to their reproductive and general health criteria. Both vaginal and semen samples were subjected to 16S rDNA sequencing to reveal the bacterial diversity and identify distinct microbial community types. Ethics statement The study was approved by the Ethics Review Committee on Human Research of Tartu University, Tartu, Estonia (protocol no. 193/T-16) on 31 May 2010. Participation in the research was voluntary. Written informed consent was obtained from all study participants. RESULTS: The men with Acinetobacter-associated community who had children in the past, had the highest ART success rate (P < 0.05). The women with bacterial vaginosis vaginal microbiome community and with L. iners-predominant and L. gasseri-predominant microbiome had a lower ART success rate than women with the L. crispatus-predominant or the mixed lactic-acid-bacteria-predominant type (P < 0.05). The 15 couples where both partners had beneficial microbiome types had a superior ART success rate of 53%, when compared with the rest of the couples (25%; P = 0.023). CONCLUSIONS: Microbiome disturbances in the genital tract of both partners tend to be associated with couple's infertility as well as lower ART success levels and may thus need attention before the ART procedure. The incorporation of genitourinary microbial screening as a part of the diagnostic evaluation process may become routine for ART patients if our results are confirmed by other studies.

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Male infertility is a commonly encountered pathology that is estimated to be a contributory factor in approximately 50% of couples seeking recourse to assisted reproductive technologies. Upon clinical presentation, such males are commonly subjected to conventional diagnostic andrological practices that rely on descriptive criteria to define their fertility based on the number of morphologically normal, motile spermatozoa encountered within their ejaculate. Despite the virtual ubiquitous adoption of such diagnostic practices, they are not without their limitations and accordingly, there is now increasing awareness of the importance of assessing sperm quality in order to more accurately predict a male's fertility status. This realization raises the important question of which characteristics signify a high-quality, fertilization competent sperm cell. In this review, we reflect on recent advances in our mechanistic understanding of sperm biology and function, which are contributing to a growing armory of innovative approaches to diagnose and treat male infertility. In particular we review progress toward the implementation of precision medicine; the robust clinical adoption of which in the setting of fertility, currently lags well behind that of other fields of medicine. Despite this, research shows that the application of advanced technology platforms such as whole exome sequencing and proteomic analyses hold considerable promise in optimizing outcomes for the management of male infertility by uncovering and expanding our inventory of candidate infertility biomarkers, as well as those associated with recurrent pregnancy loss. Similarly, the development of advanced imaging technologies in tandem with machine learning artificial intelligence are poised to disrupt the fertility care paradigm by advancing our understanding of the molecular and biological causes of infertility to provide novel avenues for future diagnostics and treatments.

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Assisted reproductive technology (ART) has experienced dramatic progress over the last 30 years, and gamete donation is routine in fertility clinics. Major advances in genetic diagnostics are part of this development due to the ability to analyze multiple genes or whole genomes fast and to an affordable prize. This requires knowledge and capability to evaluate genetic variants correctly in a clinical setting. Here we report a Menkes disease case, born after ART, where genetic screening and variant scoring failed to identify an egg donor as carrier of this fatal X-linked disorder. The gene variant is a deletion of a single base pair leading to a frameshift and premature termination of the protein, predicted to result in no or severely diminished function. The variant would be classified as likely pathogenic (class 4) and should be readily detectable by molecular genetic screening techniques. We wish to highlight this case to prevent future similar cases. IVI Igenomix has developed and embarked on an ambitious screening program to detect and prevent a large number of inherited severe childhood disorders in ART pregnancies. The company has recently achieved ISO 15189 certification with competence to evaluate and deliver timely, accurate, and reliable results. Failure to identify a pathogenic variant in the ATP7A gene leading to birth of two boys with Menkes disease invokes the required procedures to screen and detect disease-causing gene variants. This calls for ethical and legal considerations in ART diagnostics to prevent fatal errors like the present.

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BACKGROUND: Both the diagnosis and the process of undergoing fertility treatment have a considerable negative effect on a person's quality of life (QoL). The evaluation of this effect is essential to offer comprehensive and high-quality care. The FertiQoL questionnaire is the most widely used instrument to evaluate QoL in people with fertility issues. OBJECTIVE: This study is aimed at examining the dimensionality, validity and reliability of the Spanish version of the FertiQoL questionnaire in a sample of Spanish heterosexual couples undergoing fertility treatment. METHODS: FertiQoL was administered to 500 people (50.2% women; 49.8% men; average age 36.1 years) recruited from a public Assisted Reproduction Unit in Spain. In this cross-sectional study, Confirmatory Factor Analysis (CFA) was used to analyse the dimensionality, validity and reliability of FertiQoL. Discriminant and convergent validity were assessed using the Average Variance Extracted (AVE), and model reliability was shown by Composite Reliability (CR) and Cronbach's alpha. RESULTS: CFA's results support the 6-factor solution of the original FertiQoL (RMSEA and SRMR <0.09; CFI and TLI >0.9). However, several items had to be eliminated due to their low factorial weights - in particular, items Q4, Q5, Q6, Q11, Q14, Q15 and Q21. Moreover, FertiQoL showed good reliability (CR >0.7) and validity (AVE >0.5). CONCLUSION: The Spanish version of FertiQoL is a reliable and valid instrument in measuring QoL in heterosexual couples undergoing fertility treatment. The CFA confirms the original 6-factors model but indicates that by eliminating some items the psychometric properties could improve. However, further research is recommended to address some of the measurement issues.

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Sperm deoxyribonucleic acid (DNA) damage has recently emerged as one of the most controversial topics in male reproductive medicine. While level I evidence indicates that abnormal sperm DNA damage has substantial adverse effects on reproductive outcomes (including chance of pregnancy and risk of miscarriage), there is limited consensus on how sperm DNA fragmentation (SDF) testing should be performed and/or interpreted in clinical practice. In this article, we review: (1) how SDF is assessed, (2) cumulative evidence regarding its impact on reproductive outcomes, (3) methods for mitigating high SDF, and (4) the most recent practice guidelines available for clinicians regarding the use and interpretation of SDF testing.

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It is well established that there are increased pregnancy-related complications for a woman who conceives through assisted reproductive treatment (ART). Furthermore, it is known that the risk to the child born is greater, believed to be related to prematurity and growth restriction. Studies have also reported epigenetic changes in the DNA of offspring conceived through ART. In addition, it is believed that they have a greater risk of congenital malformations, although some of these risks may relate to underlying infertility, rather than the ART treatment per se. As a result, it may be expected that there is a greater risk to the longer-term health of the child who is born from ART; however, evidence about the long-term health of children conceived through ART is reassuring. Even though, it is recognised that many of the studies in this field come with limitations. Low numbers of participants is one of the major limitations, which makes subgroup analyses for diverse types of ART, or diverse types of infertility, not feasible. Furthermore, studies are often limited by short follow-up periods because of the difficulty and costs involved in longitudinal study designs. In addition, the rapid changes over time in ART limit the generalisability and significance of long-term findings. Well-designed studies investigating the long-term health outcomes of ART-conceived offspring and the potential influences of various aspects of the ART procedure, as well as studies of the potential underlying epigenetic mechanisms, are imperative. Furthermore, conclusions from childhood hospitalisation data from the United Kingdom, the long-term follow-up and quality of life study from researchers in Melbourne, and the data published from the Western Australian Growing Up Healthy Study will go a long way to help reassure current and prospective parents who may require ART to conceive.

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Abstract: The level of recognition that transgender individuals (i.e. those whose gender does not match the sex assigned at birth) enjoy in our societies has certainly made giant strides. Still, there is no denying that the far-reaching ramifications arising from choices about one's gender expression do affect vital aspects of identity in school, workplaces, and the community, and should be clearly defined and addressed by laws and policies. One of the arguments most commonly used by supporters of transgender rights relies on the concept of inalienable human rights, including the rights to live safely, freely, and without fearing discrimination. The authors have set out to succinctly outline and elaborate on the dynamics that have been shaping the legal reco-gnition of transgender individuals in light of the unique legal, social and ethical complexities that such an evolution entails. Moreover, as assisted reproduction technologies make considerable progress and innovations open up new horizons for fertility preservation and restoration, it is worth exploring how such advance can play a role in upholding the reproductive rights of transgender patients who wish to achieve parenthood, and how counseling ought to be implemented taking into account the psychological traits of transgender patients and the implications of every choice they make.

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OBJECTIVE: To evaluate the clinical and cost-effectiveness of preimplantation genetic testing for aneuploidy, social freezing, donor and autologous assisted reproductive technology (ART) treatment strategies for women aged 35-45 following 6-12 months of infertility. METHODS: Four Markov decision-analytic models comprising: (i) Preimplantation genetic testing for aneuploidy (PGT-A); (ii) autologous ART from age 40 using oocytes cryopreserved at age 32 (social freezing); (iii) ART using donated oocytes (donor ART); (iv) standard autologous ART treatment (standard care) were developed for a hypothetical cohort of 35 to 45 years old ART naïve women with 6-12 months of infertility. Input probabilities for key parameters including live birth rates were obtained from the available literature. Deterministic and probabilistic sensitivity analyses were conducted to address uncertainty in estimating the parameters and around the model's assumptions. Cost effectiveness was assessed from both societal and patient perspectives . RESULT(S): For infertile women at age 40 and above, social freezing is the most cost-saving strategy with the highest chance of a cumulative live birth at a lowest cost from a societal perspective. PGT-A and donor ART were associated with higher treatment costs and cumulative live-birth rates compared with the autologous ART. Among the four ART strategies, standard autologous ART has the lowest cumulative live birth rate of 45% at age 35 and decreasing to 1.6% by age 45 years. At a willingness-to-pay threshold of Australian dollars (A$)50,000, our model shows all alternative treatment strategies -PGT-A, social freezing and donor ART have a higher probability of being cost-effective compared to the standard autologous ART treatment. However, higher out-of-pocket expenditure may impede their access to these alternate strategies. CONCLUSION: Given current evidence, all alternate strategies have a higher probability of being cost-effective compared to the standard autologous ART treatment. Whether this represents value for money depends on societal and individual's willingness-to-pay for children conceived with ART treatment.

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Assisted Reproductive Technologies (ART) employ gamete/embryo handling and culture in vitro to produce offspring. ART pregnancies have an increased risk of low birth weight, abnormal placentation, pregnancy complications, and imprinting disorders. Embryo culture induces low birth weight, abnormal placental morphology, and lower levels of DNA methylation in placentas in a mouse model of ART. Whether preimplantation embryos at specific stages of development are more susceptible to these perturbations remains unresolved. Accordingly, we performed embryo culture for several discrete periods of preimplantation development and following embryo transfer, assessed fetal and placental outcomes at term. We observed a reduction in fetal:placental ratio associated with two distinct windows of preimplantation embryo development, one prior to the morula stage and the other from the morula to blastocyst stage, whereas placental morphological abnormalities and reduced imprinting control region methylation were only associated with culture prior to the morula stage. Extended culture to the blastocyst stage also induces additional placental DNA methylation changes compared to embryos transferred at the morula stage, and female concepti exhibited a higher loss of DNA methylation than males. By identifying specific developmental windows of susceptibility, this study provides a framework to optimize further culture conditions to minimize risks associated with ART pregnancies.

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BACKGROUND: The stress experienced during pregnancy and the decrease in marital satisfaction affects the quality of life of the woman negatively. OBJECTIVE: This study conducted to determine the quality of life and the relationship with perceived stress and marital satisfaction in pregnant women with ART. METHODS: This study is a descriptive and corelational study. The study sample consisted of 120 pregnant women with ART. The patient descriptive form, the Married Life Scale (SWML), The Perceived Stress Scale (PSS) and The Fertility Quality of Life (FertiQoL) were used for data collection in this study. RESULTS: The mean of the total score of PSS was 16.38 ± 4,721, the mean score of SWML was 23.03 ± 4.42 and the mean of the total score of FertiQoL was 81,25 ± 17,56. There was a moderate negative correlation (r = -0,551, p = 0,001) between the total score of the FertiQol and the total score of PSS and there was a moderate positive correlation (r = 0,452, p = 0,001) between FertiQol total score and SWML. CONCLUSION: This study found that the rate of perceived stress affected the quality of life negatively and marital satisfaction affected the quality of life positively in pregnant women with ART.

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Infertility is a highly relevant global issue affecting the reproductive health of at least 15% of reproductive-aged couples worldwide. The scope and severity of the infertility problem is even more prevalent in developing countries, mostly due to untreated reproductive tract infections (RTIs). Infertility, however, goes beyond the mere inability to procreate, but brings about profound psychological, social, and ethical implications of enormous magnitude. In vitro fertilization (IVF) and other assisted reproduction technologies (ARTs) have gradually become widespread therapeutic options. After all, the implementation of medically assisted reproductive procedures in order to overcome infertility is in keeping with the tenets of the reproductive rights agenda laid out at the International Conference on Population and Development (ICPD) in Cairo in 1994. Nonetheless, concerns still linger about how to implement and regulate such interventions in an ethically tenable fashion. The unremitting pace at which such techniques develop have upset the very notion of sexuality relating to reproduction as well as the concept of family itself. That rift risks causing a crisis in terms of bioethics sustainability and enforcement, which is bound to happen when science and innovation outpace the bioethical precepts on which we rely for essential guidance in medical practice. The authors argue in favor of an approach to regulation and policy-making that puts on the forefront a thorough assessment as to potential risks that such interventions might entail for foundational bioethics principles and inalienable human rights.