Search

Infertility treatment is a possible factor in hypertensive disorders of pregnancy (HDP). Identifying the characteristics of pregnant women who have undergone infertility treatment and have a potential risk for HDP is valuable for its prevention and treatment. Using data from 12,456 pregnant Japanese women from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, the association between infertility treatment and HDP was analyzed. A multiple logistic regression model showed an association between infertility treatment and HDP (odds ratio, 1.34; 95% confidence interval, 1.05–1.72). In vitro fertilization/intracytoplasmic sperm injection were also associated with HDP. Moreover, these associations were observed even among women who were not overweight and did not smoke. The application of infertility treatment should be carefully considered, even among women with low modifiable risk factors.

STUDY QUESTION Is geographic proximity to a fertility clinic associated with the likelihood of women of reproductive age undertaking different forms of medically assisted fertility treatment? SUMMARY ANSWER After adjusting for socioeconomic status (SES) and other confounders including a proxy for the need for infertility treatment, women who lived within 15 km of a fertility clinic were 21% more likely to undergo ART treatment and 68% more likely to undergo IUI treatment than those who lived further than 60 km away. WHAT IS KNOWN ALREADY In most countries, patients living outside of metropolitan areas are more likely to be more socio-economically disadvantaged and to have less equitable access to healthcare. However, how a woman’s residential proximity to fertility clinics predicts utilization of high-cost/high-technology treatment (ART) and low-cost/low-technology treatment (IUI) is limited, and whether socio-economic disadvantage explains much of the hypothesized lower utilization is unknown. Australia’s universal insurance scheme provides supportive reimbursement for almost all ART and IUI treatment regardless of age or number of cycles, providing a unique setting to investigate disparities in access to infertility treatment. STUDY DESIGN, SIZE, DURATION National population-based observation study of ART and IUI treatment utilization by women across socio-economic gradients and Australian residential locations between August 2015 and December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Universal insurance claims information on female patients who underwent ART or IUI were provided by Services Australia, comprising 67 670 female patients who accessed 162 795 ART treatments, and 10 211 female patients who accessed 19 615 IUI treatments over a 29-month period. Incidence rates by SES and proximity to fertility clinics were calculated to describe the number of women undergoing at least one ART or IUI treatment cycle per 1000 women of reproductive age (25–44). Treatment frequencies were calculated to describe the average number of ART or IUI treatment cycles per woman of reproductive age who had undergone at least one ART or IUI treatment during the study period. Poisson regression analyses were used to estimate the independent effect on accessibility to infertility treatment by geographic proximity (based on small area locations) to the closest fertility clinic after adjusting for SES, childbearing delay, remoteness area, and marital status. MAIN RESULTS AND THE ROLE OF CHANCE On average, 19.1 women per 1000 women of reproductive age underwent at least one fresh or frozen ART cycle, with an average 2.3 ART cycles each, while 3.0 women per 1000 women of reproductive age received at least one IUI cycle, with an average of 1.6 IUI cycles each. After adjusting for SES and other confounders including a proxy for the need for infertility treatment, women who lived within 15 km of a fertility clinic were 21% more likely to undergo ART treatment and 68% more likely to undergo IUI than those who lived over 60 km away. Regardless of geographic location, there was a steady and independent gradient in access to ART treatment based on increasing SES, with women residing in the most advantaged residential quartile having a 37% higher rate of receiving ART treatment compared to those in the most disadvantaged quartile. The negative effect of social disadvantage on ART use became more pronounced as distance from a fertility clinic grew, indicating that the barriers to access to ART care caused by distance were further compounded by the level of socioeconomic advantage of the women’s residential location. In contrast, socioeconomic status did not modify the likelihood of using IUI over and above the distance from a fertility clinic. In relation to IUI treatment, differences in utilization by SES disappeared after adjusting for geographic proximity to a fertility clinic, childbearing delay, remoteness area, and marital status. LIMITATIONS, REASONS FOR CAUTION Information is aggregated by small geographic areas and it therefore may not reflect individual characteristics. Australia provides partial but comparably supportive reimbursement for both ART and IUI through its universal healthcare system and thus the results may not be fully generalizable to other settings. WIDER IMPLICATIONS OF THE FINDINGS Residential proximity to a fertility clinic is a persistent barrier to accessing ART and IUI treatment, regardless of SES, even in countries characterized by supportive public funding, such as Australia. SES is less of a barrier to accessing IUI than ART, presumably driven by the lower cost and fewer clinic visits required with IUI treatment. Safe and effective fertility treatment should be available to all women regardless of where they live. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Australian National University Research scholarship and by the Higher Degree Research Fee Merit Scholarship. The authors have no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

Women with Turner syndrome (TS) are subfertile due to premature ovarian insufficiency. Most women require hormone replacement therapy for attaining menarche and assisted reproductive technology (ART) using donor oocytes, autologous oocytes or in-vitro fertilisation for conception. Irrespective of the karyotype, monosomy X (45, X) or mosaic pattern, women with TS hold a very high risk for pregnancy due to high mortality rate secondary to aortic dissection and severe pre-eclampsia. Such high-risk pregnancies mandate extensive prepregnancy counselling, the need for multidisciplinary teams, close surveillance and follow-up to attain a successful outcome. In this article, we report one such case of pregnancy in a woman with TS carrying a twin gestation following ART with donor oocyte.

International audience; Purpose: Infertility in adolescents and young adult (AYA) survivors of malignant disease remains a major long-term adverse effect, but semen collection for fertility preservation in fertility centers is not always feasible and makes AYAs uncomfortable. We evaluated the feasibility of collecting sperm samples on the ward versus in fertility centers. Methods: Consecutive hospitalized AYA-aged male patients in the Hematology AYA unit (Saint-Louis Hospital, France) between August 2010 and June 2016 with hematological disease and indication of semen collection (n = 95) were included in this retrospective study. Semen quality was analyzed according to World Health Organization guidelines and was compared according to semen collection place: on the ward (n = 46) or in fertility center (n = 49). Results: The median age was median age 19.1 years (range: 13.7-33.3; interquartile range: 17.1-22.8) and 85 patients successfully collected semen. Sperm collection failure was ∼11% and was comparable between the two modalities as were main sperm quality characteristics (semen volume, sperm concentration, total sperm count, progressive motility and vitality, sperm morphology, and multiple anomalies index). Oligospermia was significantly higher in the samples obtained in fertility center (47.7%) than on the ward (26.8%), p = 0.047. Average frozen straws were comparable, 12.2 ± 6.4 on the ward versus 11.9 ± 6.3 in fertility center. Conclusion: Semen collection on the ward is feasible and would be particularly interesting for AYA male patients without altering semen quality characteristics.

Background Children conceived through assisted reproduction are at an increased risk for growth and genomic imprinting disorders, often linked to DNA methylation defects. It has been suggested that assisted reproductive technology (ART) and underlying parental infertility can induce epigenetic instability, specifically interfering with DNA methylation reprogramming events during germ cell and preimplantation development. To date, human studies exploring the association between ART and DNA methylation defects have reported inconsistent or inconclusive results, likely due to population heterogeneity and the use of technologies with limited coverage of the epigenome. In our study, we explored the epigenetic risk of ART by comprehensively profiling the DNA methylome of 73 human cord blood samples of singleton pregnancies (n = 36 control group, n = 37 ART/hypofertile group) from a human prospective longitudinal birth cohort, the 3D (Design, Develop, Discover) Study, using a high-resolution sequencing-based custom capture panel that examines over 2.4 million autosomal CpGs in the genome. Results We identified evidence of sex-specific effects of ART/hypofertility on cord blood DNA methylation patterns. Our genome-wide analyses identified ~ 46% more CpGs affected by ART/hypofertility in female than in male infant cord blood. We performed a detailed analysis of three imprinted genes which have been associated with altered DNA methylation following ART (KCNQ1OT1, H19/IGF2 and GNAS) and found that female infant cord blood was associated with DNA hypomethylation. When compared to less invasive procedures such as intrauterine insemination, more invasive ARTs (in vitro fertilization, intracytoplasmic sperm injection, embryo culture) resulted in more marked and distinct effects on the cord blood DNA methylome. In the in vitro group, we found a close to fourfold higher proportion of significantly enriched Gene Ontology terms involved in development than in the in vivo group. Conclusions Our study highlights the ability of a sensitive, targeted, sequencing-based approach to uncover DNA methylation perturbations in cord blood associated with hypofertility and ART and influenced by offspring sex and ART technique invasiveness.

Male infertility is a disease that deserves greater clinical attention and research. A universally accepted definition that emphasizes the modulatory impact of age, lifestyle and environmental factors and includes comprehensive diagnostic and treatment guidelines is needed to ensure accurate evaluation and effective care. Accordingly, male infertility should be defined as a disease of the male reproductive system, caused primarily by congenital and genetic conditions, anatomical, endocrine, functional or immunological abnormalities of the reproductive system, genital tract infections, cancer and its related treatments, and sexual disorders incompatible with intercourse. Inadequate lifestyle, exposure to toxicants and advanced paternal age are critical factors acting alone or exacerbating the impact of known causative factors. The focus on male infertility must be balanced with that on female infertility to ensure the best possible outcome for the couple. Fertility clinics are encouraged to prioritize collaboration with reproductive urologists and andrologists to provide the best possible care for male infertility patients.

Reproductive health technology allows married couples who experience infertility to have a child through assisted reproductive technology (ART), such as the in vitro fertilisation (IVF) process. The transfer of the extracted embryo to the woman’s womb is called surrogacy technology (gestational surrogacy). The legality of the practice of surrogacy is still questionable, both on a national and international level. This research discussed the legality of surrogacy in some religious countries, focusing on Indonesia. This research used normative juridical research methods or literature review through a comparative religion-legal approach. This study indicated that most do not have a specific legal instrument regarding surrogacy practice. International law also does not have a standard legal instrument regarding the legality of surrogacy. Legality is determined by each religious country’s national laws and customs. For example, Indonesian law prohibits this practice implicitly under Law No. 36 of 2009 concerning health. The United Kingdom legalised surrogacy through the Surrogacy Agreement Act 1985, which was amended to the Human Fertilization and Embryology Act 2008, Greece through the Greek Legislation Law 3089/2002 and Law 3305/2005, and India through the 2019 Surrogacy Regulation Bill. Those countries have their limitations and characteristics that rule surrogacy. Surrogacy is indeed a technological advancement in the health sector. However, for countries that are influenced much by religion, technological advances sometimes conflict with the culture and the belief that has long been followed by most of the population. For Indonesia, the largest of Sunni Islam ruled surrogacy against the law. Next, Iran, as a Shia Islam country, ruled that surrogacy is a legal action. Contribution: The research provided information and knowledge regarding the different settings of surrogacy practice. Most religious countries bravely rejected or put strict limits on the practice of surrogacy.

Purpose: The aim of this narrative review is to offer an overview about the role of progesterone levels on pregnancy outcome in patients undergoing assisted reproductive technologies (ARTs). Methods: A detailed computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science) to determine the importance of elevated progesterone levels at different stages of the cycle for pregnancy rates in the in vitro fertilization (IVF) cycle. Our review also provides information on the differences between elevated progesterone levels and their interpretation in normal and in poorly responding women. Results: After careful evaluation, our search strategy yielded a total of 15 included articles, showing the possible factors that may have had an impact on the increased progesterone level before human chorionic gonadotropin (HCG) injection and the different thresholds above which the pregnancy rate was lower. Furthermore, increased progesterone on cycle day 2 or 3 could serve as a marker for increased progesterone in the late follicular phase, which is associated with a lower pregnancy rate. Conclusion: Despite the literature data that support the negative effect of elevated progesterone on fresh cycles, due to lack of randomized controlled trials, the value of measuring progesterone in daily practice is questionable. Available evidence supports the detrimental effect of elevated progesterone in different subgroups of women, although there is still the need for defining different thresholds and durations of high progesterone exposure. The need for various thresholds for different cohorts of women, the inter-assay variability is making this decision harder.

Background : The gonadotrophin-releasing hormone agonist (GnRHa) has gained widespread popularity of achieving pituitary suppression before ovarian stimulation with exogenous gonadotropins in assisted reproductive technology protocols. However, a very small part of patients may develop ovarian hyperresponse after the sole administration of GnRHa without gonadotropins. Case report: A 32-year-old female diagnosed with polycystic ovary syndrome presented for her second IVF cycle in our reproductive center. Twenty-eight days after 3.75mg triptorelin was administrated on day 2 of her menstrual cycle, bilateral ovaries were significantly enlarged and presented multiple cystic masses. The hormone profile was as follows: E2＞4870pg/ml, P 13.19ng/ml, FSH 14IU/L, and LH 10.77IU/L. The patient felt symptoms of mild ovarian hyperstimulation syndrome. In the subsequent IVF treatment cycle, antagonist protocol was performed. It showed that follicles developed slowly and exogenous gonadotropins were used for 13 days. Finally, seven oocytes were obtained and only one blastocyst graded 4BC formed. Conclusion: Ovarian hyperstimulation following the sole administration of GnRHa can be occurred, but the mechanism is still not yet clear. Antagonist protocol may be an alternative fertility strategy, but the risk of poor embryo quality and low pregnancy rate of transplantation should be warned.

Conceptualizations of the ‘biological clock’ in popular imaginary in the USA centre on the temporal limits of fertility, with assisted reproductive technology (ART) an increasingly proposed answer to these constraints (at least in the public imaginary). In this study, I analyse how surrogates in the USA understand their own bioavailability for others’ reproductive needs in the commercial ART market vis-a-vis their own reproductive trajectories. Based on interview data with gestational surrogates, I propose a new concept of the ‘ART clock’ to capture how time shapes the experiences of reproductive workers in the US fertility clinic. My findings point to four important ART time-related issues: (i) women desiring to extend their own ‘biological clocks’ via surrogacy; (ii) significant time being needed to achieve and sustain third-party pregnancy; (iii) women extending their total reproductive time via repeat surrogacy ‘journeys’; and (iv) temporal constraints to surrogacy reproduction regarding time of year, the day-to-day time effort, the number of surrogacy journeys, the total number of pregnancies, and surrogates’ age and the ages of their children. Each of these aspects point to important ways that reproductive desire and time shape the labour of reproductive workers, highlighting temporal constraints to assisted reproduction and limits to ART as a solution to delayed reproduction and the biological clock.

Infertility clinics and providers in the United States have made efforts to become LGBTQ-inclusive, yet patients in same-sex partnerships continue to face disproportionate barriers to accessing fertility services when pursuing parenthood. This narrative case study of a same-sex couple’s “labor to conceive” illustrates some of the structural barriers to family building that lesbian mothers face when seeking fertility care, including insurance coverage of fertility treatments, federal regulations for sperm donation, and legal definitions of parenthood. Exclusionary medical and legal systems are discussed, as are the informal strategies that this same-sex couple utilized to negotiate and circumvent these barriers. A patient-centered model of advocacy that facilitates access to and protection of same-sex partners seeking (in)fertility services is presented. Intervention points at the (1) Logistical and (2) Societal levels are considered with respect to three domains of same-sex reproduction: (A) insurance; (B) sperm donation; (C) legal adoption.

Objective To assess the occurrence of spontaneous pregnancy after a history of total bilateral salpingectomy (BS). Data Sources A systematic search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching MEDLINE, Embase, Google Scholar, PubMed, SCOPUS, and Web of Science from database inception to February 20, 2020. Methods of Study Selection We included women with a history of total BS for any indication with subsequent spontaneous pregnancy. Excluded were women who had a history of incomplete/partial salpingectomy or tubal occlusion, who had pregnancy after assisted reproductive technology, and whose pregnancy was not appropriately confirmed via beta-subunit of human chorionic gonadotropin or ultrasound. Tabulation, Integration, and Results The systematic search retrieved 1942 articles; 39 studies were potentially eligible, and their full texts were reviewed. A total of 4 case reports were included. Total BS had been performed for other indications than permanent contraception in all cases. Pain was the most common presenting symptom. All 4 pregnancies were intrauterine in location. Treatment was based on desire to continue pregnancy and hemodynamic stability. Conclusion Spontaneous pregnancy after total BS is exceedingly rare. The present data suggest that it is reassuring to offer total BS as a form of permanent contraception. Prospective data are warranted to ascertain short- and long-term effects of total BS for permanent contraception including its efficacy.

Objective To develop in vitro fertilization (IVF) prediction models to estimate the individualized chance of cumulative live birth at two time points: pretreatment (i.e., before starting the first complete cycle of IVF) and posttreatment (i.e., before starting the second complete cycle of IVF in those couples whose first complete cycle was unsuccessful). Design Population-based cohort study. Setting National data from the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System. Patient(s) Based on 88,614 women who commenced IVF treatment using their own eggs and partner’s sperm in SART member clinics. Intervention(s) Not applicable. Main Outcome Measure(s) The pretreatment model estimated the cumulative chance of a live birth over a maximum of three complete cycles of IVF, whereas the posttreatment model did so over the second and third complete cycles. One complete cycle included all fresh and frozen embryo transfers resulting from one episode of ovarian stimulation. We considered the first live birth episode, including singletons and multiple births. Result(s) Pretreatment predictors included woman’s age (35 years vs. 25 years, adjusted odds ratio 0.69, 95% confidence interval 0.66–0.73) and body mass index (35 kg/m2 vs. 25 kg/m2, adjusted odds ratio 0.75, 95% confidence interval 0.72–0.78). The posttreatment model additionally included the number of eggs from the first complete cycle (15 vs. 9 eggs, adjusted odds ratio 1.10, 95% confidence interval 1.03–1.18). According to the pretreatment model, a nulliparous woman aged 34 years with a body mass index of 23.3 kg/m2, male partner infertility, and an antimullerian hormone level of 3 ng/mL has a 61.7% chance of having a live birth over her first complete cycle of IVF (and a cumulative chance over three complete cycles of 88.8%). If a live birth is not achieved, according to the posttreatment model, her chance of having a live birth over the second complete cycle 1 year later (age 35 years, number of eggs 7) is 42.9%. The C-statistic for all models was between 0.71 and 0.73. Conclusion(s) The focus of previous IVF prediction models based on US data has been cumulative live birth excluding cycles involving frozen embryos. These novel prediction models provide clinically relevant estimates that could help clinicians and couples plan IVF treatment at different points in time.

Purpose: It was aimed to compare the adaptation to pregnancy in women who received infertility treatment and those who didn't. Methods: A total of 174 pregnant women were included in the study, 51 in the group that received infertility treatment and 123 in the group that did not. The data were collected with the Personal Information Form including the descriptive characteristics and the Prenatal Self-Evaluation Questionnaire (PSEQ). Results: The mean age of the pregnant women who received infertility treatment was 33.73±5.79 years, while it was 28.89±4.12 years for those who didn't. Although the mean total score of PSEQ was lower in pregnant women receiving infertility treatment, the difference was not found to be statistically significant. In the group that became pregnant with the infertility treatment, the subdimension score of "thoughts about the well-being of self and baby" was found to be higher, while the scores of subdimensions "acceptance of pregnancy", "readiness for labour" and "control in labour" were lower. Conclusion: In the study, the adaptation to the pregnancy of both groups was found to be similar. On the other hand, pregnant women who received infertility treatment were found to have lower adaptation to the thoughts about the wellbeing of self and baby sub-dimension, and higher adaptation to the identification with the role of motherhood, preparation for labour and control in labour subdimensions.

What is the impact of high serum anti-Müllerian hormone (AMH) concentrations on fertilization and embryo development among infertile women undergoing treatment with assisted reproductive technology (ART)?Retrospective study of 1036 infertile women undergoing ART; women were divided into three groups according to serum AMH concentrations: AMH1.1 ng/ml, 1.1-5.0 ng/ml and5.0 ng/ml. The fertilization and embryo development rates of patients with different AMH concentrations and after stratification according to age were compared.Women with high AMH concentrations were younger and had higher testosterone concentrations (0.4 ± 0.13 versus 0.3 ± 0.12 versus 0.3 ± 0.08 µg/dl, P 0.001) than women with low AMH concentrations. However, analysis of the embryo development rate showed negative outcomes for women with high AMH concentrations, including a poor fertilization rate (76.3 ± 17.36 versus 82.1 ± 19.15 versus 82.4 ± 25.38, P = 0.003), and poor day 3 embryo development rate (55.6 ± 23.88 versus 62.6 ± 26.52 versus 62.8 ± 32.65, P = 0.014). Multivariate linear regression analysis showed significantly negative correlations of the AMH concentrations with the fertilization rate (P 0.001) and day 3 embryo development rate (P = 0.006). Subgroup analysis showed that age 30 years or younger had a significant negative correlation with AMH and the embryo development rate, including the fertilization rate (P 0.001) and day 3 embryo development rate (P = 0.037).These results suggest that high serum AMH concentrations, contributing to a hyperandrogenic environment and leading to decreased oocyte developmental competence, may have a negative impact on fertilization and the early stage of embryo development in women undergoing treatment with ART.

Oocyte and embryo grading is one of the most important steps in assisted reproductive technology to identify the best among cultured embryos for transfer or vitrification. The most commonly used non-invasive method is morphological assessment of gametes and embryos using a microscope. This method despite being simple and cost-effective has interobserver and intraobserver variability and subjectivity and has little to offer about the physiological state of embryos. This review sourced research articles and reviews pertaining to other non-invasive assessment methodologies from Medline and PubMed to collate latest technologies in vogue and identify novel methodologies of the future. The review assesses the current understanding in oocyte and embryo grading and touches upon novel non-invasive techniques and potential biomarkers to identify the best embryo. The latest available literature on time-lapse imaging, hierarchical algorithms, omics (consisting of proteomics and secretomes), miRNAs, mitochondrial RNAs and artificial intelligence has been accessed to summarize the enormous information available, to identify gaps in current interpretations, to identify emerging technologies and to provide direction for future research. This review will greatly benefit anyone practicing assisted reproduction and clinical embryology.

Objective Initially developed for sperm abnormalities, the indications of intracytoplasmic sperm injection (ICSI) have progressively expanded beyond male factor infertility, but the benefit of ICSI over conventional in vitro fertilisation (IVF) in terms of live birth rate (LBR) in non-male factor infertility has not been formally demonstrated in the literature. The aim of this systematic review and meta-analysis was to determine whether the use of ICSI improves LBR as compared to IVF in non-male factor infertility cases. Evidence review This prospectively registered systematic review and meta-analysis was guided by PRISMA guidelines. PubMed, Embase, Cochrane Library were searched for relevant literature reported between January 01, 2004 and March 15, 2020. Only articles conducted in couples without obvious male factor infertility according to the authors were included. Live Birth Rate (LBR) per cycle and/or per transfer was used as main outcome. Fertilisation rate, cycles with total fertilisation failure, and clinical pregnancy rate were also recorded as secondary outcomes. Study selection, bias assessment and data extraction were performed by two independent reviewers. The methodological quality of the selected studies was assessed by two independent reviewers using the Cochrane Handbook methods and by the adapted Newcastle-Ottawa Quality Assessment Scale for cohort studies. The risks of bias were assessed using ROBIN-1 tools. Risk ratio and 95% confidence interval (CI) were estimated using random effect model. Results Among the 1,760 potentially eligible studies, 61 were fully assessed and 21 were included in the meta-analysis, corresponding to almost 1,000,000 assisted reproductive technology cycles. Among the selected studies, 17 reported LBR per cycle, 11 reported LBR per transfer, and 7 among them reported both outcomes. One was a prospective randomised controlled trial, while others were either retrospective cohort (n=17) or case-control studies (n=4). Individual studies’ sample size ranged from 60 to 569,605 cycles. Meta-analysis showed that IVF provided a significantly higher LBR per cycle when compared to ICSI (RR=1.10; 95%CI=1.02-1.18). LBR per transfer tended to be higher when IVF was used as compared to ICSI, but this difference barely reached statistical significance (RR 1.18, 95% CI 1.00-1.38, p=.05). Subgroup analysis performed in poor responders showed no significant difference between IVF and ICSI concerning LBR per cycle or LBR per transfer. Secondary analyses demonstrated a lower fertilisation rate, but comparable clinical pregnancy and fertilisation failure rate with IVF as compared to ICSI. Sensitivity analyses led to similar results and conclusions. Conclusion Despite its limitations, mainly related to the inclusion of a majority of retrospective studies, this meta-analysis synthesizes and reinforces the existing literature and provides further evidence that ICSI does not improve LBR per cycle / per transfer as compared to IVF in couples undergoing assisted reproductive technology for non-male infertility.

Investigating the experiences of healthcare providers affected by infertility in the United States: a scoping review protocol

Investigating the experiences of healthcare providers affected by infertility in the United States: a scoping review

Background: Assisted reproductive technology, one of which is intrauterine insemination (IUI) allows infertile couples to get pregnant. The pregnancy success of IUI procedure varies among individuals. Objective: The study aim is to determine whether there is a relationship between smoker male partners and IUI success. Methods: This research is an analytic study with cross-sectional approach conducted at Kasih Ibu General Hospital Denpasar with purposive sampling technique. There are 35 male couples aged 25-50 years who underwent the IUI procedure selected as samples. The research data was gathered from patient's medical records and statistically analyzed using the Chi-Square test. Results: The study found that of the 35 samples, 13 (37.1%) were smokers, whereas 22 (62.9%) male partners were non-smokers. There were 6 (17.1%) samples’ partners who were pregnant after undergoing the IUI procedure, and 29 (82.9%) samples’ partners were not pregnant. It was found that there was no significant relationship between male partner smokers and the success of IUI at Kasih Ibu General Hospital Denpasar (p=0.832). However, in descriptive analysis and relative risk calculation, smoker male partner is less likely to achieve pregnancy than non-smoker’s male partner (RR=0.85). Conclusion: Smoker male partners may not contribute to IUI success. Further studies should be done with a higher number of samples, multicenter, and more controlled risk factors to make it more accurate in determining the relationship.

AIM The effect of placenta previa on age-specific placental size has not yet been elucidated. This study aimed to examine the effect of placenta previa on the Japanese standardized z-scores of placental size. METHODS This retrospective cohort study included Japanese participants from Ohta Nishinouchi Hospital with single pregnancies who gave birth during 2013-2019. The participants were categorized into two groups based on the presence or absence of placenta previa. Multiple linear regression analyses were used to identify the association of placenta previa with the z-score of placental size, after adjusting for factors, such as maternal smoking status, maternal age, assisted reproductive technology, myoma uteri, uterine anomaly, maternal hypertension at the time of pregnancy, and body mass index before pregnancy. RESULTS A total of 4071 Japanese women (76 with placenta previa and 3995 without placenta previa) were identified. Placenta previa significantly increased the placental weight z-score (partial regression coefficient: 0.44, 95% confidence interval 0.10-0.70, p

Recurrent implantation failure is a major problem in assisted reproductive technology (ART). Although ART systems have evolved rapidly over the decades, it is still difficult to diagnose uterine conditions suitable for embryo transfer (ET) without the use of invasive endometrial procedures. Previous studies in mice showed that leukemia inhibitory factor (LIF) is a well-known endometrial biomarker for uterine implantation capacity, also known as uterine receptivity. This study focused on LIF in the mouse and human cervix as a possible biomarker of implantation capacity. We found that high expression of LIF in the cervical epithelium is strongly correlated with that of the uterine epithelium during the peri-implantation period in mice. Likewise, human cervical epithelia also exhibit elevated levels of LIF in the peri-implantation period. In addition, cervical LIF is downregulated in mice with defective implantation caused by pharmacological treatments. These results indicated that cervical LIF is a possible biomarker that detected uterine receptivity without invasive endometrial damage.

Objective: In this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes. Methods: A prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses. Results: In the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients. Conclusions: Baseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS; this possibility should be confirmed in further research.

Background: Sperm-associated antigens (SPAGs) are 18 types of proteins, some of which play important roles in various biological functions associated with assisted reproductive technology outcomes,...

Research question What are the reproductive choices and retrospective reflections of women at least 4 years after planned oocyte cryopreservation (POC)? Design This was an internet survey, using the REDCap application, of women who underwent POC, at a single-centre university-affiliated IVF unit, 4–8 years before the survey. The questionnaire addressed reproductive choices and outcomes following POC. Results Seventy-nine women who underwent POC during 2011–2014 were invited to participate, and 70 (89%) responded. Mean age at cryopreservation was 37.1 ± 2.4 (range 30–41) years, mean age at study participation 42.6 ± 2.6 (range 35–48) years, and mean time from first cryopreservation cycle to study participation 5.5 ± 1.3 (range 4–8) years. The main retrospectively reported reason for POC was not wanting to become pregnant without a partner (59, 84%). During the follow-up period, 44 women (63%) attempted to conceive either naturally or by assisted reproductive technology using fresh or cryopreserved oocytes. Of those, 28 women achieved a live birth (64% of those who tried to conceive). Fourteen respondents (20% of all respondents) reported using their cryopreserved oocytes, and three (21%) achieved a birth using those oocytes. Fifteen women (34%) of those who tried to conceive used donor spermatozoa. Conclusions The most common reasons for not using frozen oocytes were achieving pregnancy without frozen oocytes or preferring not to have a child without a partner. A considerable proportion of women who had POC and were not interested in being a single parent by choice eventually try to conceive using donor spermatozoa several years later.

Objective To determine the association of combined parental preconception overweight and obesity on infant birthweight. Design Retrospective study of fresh in vitro fertilization or intracytoplasmic sperm injection cycles (2009–2017). Setting Repromed, South Australia, assisted reproductive technology clinic. Patients Couples undergoing in vitro fertilization/intracytoplasmic sperm injection insemination with their own gametes and transfer of a fresh single blastocyst (N = 1,778). Intervention(s) None. Main Outcome Measures Parental body mass index (BMI) was recorded prior to cycle initiation. Infant birthweight was recorded at delivery. The impact of parental obesity and their interaction on first singleton term (≥37 weeks’ gestation) birthweight was assessed using linear regressions assessing nonlinearity and a pairwise linear interactions. Results In the base model where parental BMI is assumed linear, there was strong evidence for higher birthweight with increasing maternal BMI (11.2 g per maternal kg/m2; 95% confidence interval, 7.2, 15.1) but not paternal BMI. The inclusion of a pairwise linear interaction indicated that paternal BMI attenuates the positive association between maternal BMI and infant birthweight (interaction −0.88; 95% confidence interval, −1.49, −0.27). The inclusion of nonlinear maternal BMI terms did not change the conclusions. Conclusions Increases in the mean infant birthweight associated with maternal obesity are attenuated when the father is obese. While maternal BMI contributed more to the mean infant birthweight than paternal BMI, a couple-centered approach to preconception health advice is recommended, given the documented relationships between parental obesity and childhood weight beyond infancy. Further studies in both assisted reproductive technology and general population cohorts assessing the parental BMI interaction on infant birthweight are warranted.

Assisted Reproductive Technology by means of oocyte donation is a very successful method leading to psychosocial consequences in donors. The aim of the present study was to conduct a systematic review of the existing literature on the psychosocial consequences of oocyte donation in the donors. The present study was conducted as a systematic review based on the PRISMA checklist. Searches were performed in PubMed, Web of Science, Scopus, and SID databases for the documents written between 2000 and 2020 regardless of the research methodology and the employed tools. English and Persian articles focusing on psychological and social issues of oocyte donation were reviewed. From 2,759 studies which were found, finally 14 related ones were selected. Psychosocial challenges of donors were obtained in three dimensions including short-term and long-term psychological reactions to treatment complications, emotional reactions to their function as an oocyte donor, and emotional reactions to the resulting offspring resulting and related social challenges. According to the existing studies, oocyte donation is a challenging process with short-term and long-term psychosocial consequences for donors. In order to prevent the feasible psychosocial hazards caused by the donation process, it is necessary to provide oocyte donors with psychosocial support, proper counseling, and awareness of the facts and possible issues ahead.

People with cystic fibrosis (pwCF) have experienced increased survival and wellbeing in recent decades, such that more than half of those living with CF are adults. Consequently, sexual and reproductive health is increasingly important for pwCF, because many are considering parenthood. Most men and some women with CF (wwCF) will have reduced fertility, which in both sexes is multifactorial. However, unplanned pregnancies in women are not rare, and contraception and its interaction with CF complications need to be addressed by the CF team. Reduced fertility may be overcome in most pwCF through use of assisted reproductive technologies; however, the risk of having offspring with CF must be considered. Most wwCF will have normal pregnancies, but premature birth is common, especially in the setting of reduced lung function and CF-related diabetes (CFRD); optimization of treatment is recommended during pregnancy planning. Parenting imposes an increased burden on pwCF, with the challenges of caring for the newborn, postpartum physiologic changes, and maintaining CF treatments. Most drugs used to treat CF are considered safe in pregnancy and lactation, but exceptions need to be acknowledged, including the limited data regarding safety of CF transmembrane conductance regulator (CFTR) modulators during conception, pregnancy, and lactation. Because most pwCF are eligible for highly effective CFTR modulators, fertility, contraception, and pregnancy in people with CF is changing. Prospective studies regarding these issues in people treated with CFTR modulators are paramount to provide evidence-based guidance for management in the current era of CF care.

The prevalence of maternal cardiovascular disease (CVD) has risen throughout the developed world, reflecting an increase in acquired cardiovascular risk factors, such as hypertension and diabetes, and the improved life expectancy of those living with congenital CVD due to advances in care. Because many cardiovascular risk factors or cardiovascular conditions are associated with infertility, reproductive-aged women with CVD may increasingly seek reproductive assistance. The worldwide use of assisted reproductive technologies (ART), such as in-vitro fertilization (IVF) with or without intracytoplasmic sperm injection, or intrauterine insemination following pharmacological ovulation induction have increased steadily over the last several decades. It is incumbent among providers who care for reproductive-aged women with pre-existing CVD or CVD risk factors to understand and appreciate the types of treatments offered and inherent risks related to infertility treatments, in order to guide their patients to making safe reproductive choices in line with their values and preferences. While infertility treatments increase the risk of complicated pregnancy, whether these risks are compounded among individuals with pre-existing CVD is less well known. In this review, we summarize current available evidence regarding short-term and long-term cardiovascular implications of ART among individuals with and without CVD, as well as treatment considerations for these women. Existing knowledge gaps and priority areas for further study are presented.

Background Research to date suggests that couples undergoing assisted reproductive technology (ART) are at a high risk of experiencing sexual difficulties. Aim This dyadic cross-sectional study aimed to provide a better understanding of the infertility-specific personal (ie, emotional, mind-body) and relational stressors associated with the sexual desire, orgasm, arousal, and sexual satisfaction of infertile couples seeking ART. Methods The sample included 185 mixed-sex infertile couples seeking ART. Participants completed online the Fertility Quality of Life tool and either the Female Sexual Function Index or the International Index of Erectile Function. Data were analyzed using path analyses based on the Actor-Partner Interdependence Model. Outcomes Individuals’ own and their partners’ sexual function (desire, orgasm, arousal domains) and sexual satisfaction. Results For men and women, infertility-related emotional stressors were associated with their own and their partner's lower sexual desire. For women, experiencing greater infertility-related emotional stressors was also associated with their partner's lower sexual satisfaction. While experiencing greater infertility-related mind-body stressors was not associated with men and women's own sexual desire, arousal, orgasm, and satisfaction, for women, it was associated with their partner's lower sexual arousal. Lastly, for men and women, infertility-related relational stressors were associated with their own lower sexual arousal, as well as with their own and their partner's lower sexual satisfaction. For women, experiencing greater relational stressors was also associated with their own lower sexual desire and orgasm. Clinical Implications Interventions addressing the emotional, mind-body, and relational spheres of infertile couples seeking ART may help facilitate improvements in sexual function and satisfaction and better serve their needs. Strengths & Limitations This study included a large sample of couples. Our sample was heterogeneous with regards to couples’ cause of infertility and treatment stage. The use of an infertility-related measure allowed us to better capture personal and relational stressors specific to couples seeking ART. Given the cross-sectional design of our study, causality between infertility-related stressors and sexual function and satisfaction cannot be inferred. Our sample included predominantly White, mixed-sex individuals with a high level of education, which may reduce the generalizability of our findings. Conclusion Couples’ subjective experience of infertility and treatment (personal and relational stressors) seems to be strongly associated with their sexual health, allowing us to identify potential targets of intervention with couples seeking ART. S.E. Amiri, A Brassard, N.O. Rosen, et al. Sexual Function and Satisfaction in Couples with Infertility: A Closer Look at the Role of Personal and Relational Characteristics. J Sex Med 2021;XX:XXX–XXX.

Objective To investigate whether there is a difference in the ectopic/heterotopic pregnancy rate of blastocyst-stage frozen-thawed embryo transfers (FETs) compared with that of cleavage-stage FETs. Design A retrospective cohort study. Setting Not applicable. Patient(s) Women undergoing autologous FETs at either the blastocyst stage (n = 118,572) or the cleavage stage (n = 117,619), as reported to the Society for Assisted Reproductive Technology from 2004 to 2013. Intervention(s) None. Main Outcome Measure(s) Pregnancy outcomes, specifically ectopic pregnancy rates and heterotopic pregnancy rates. Result(s) Among those who became pregnant, there was a significantly lower incidence of ectopic/heterotopic pregnancies in blastocyst-stage FETs versus that in cleavage-stage FETs (0.8% vs. 1.1%). The differences in ectopic/heterotopic pregnancy rates remained statistically significant after controlling for confounders such as tubal factor infertility and number of embryos transferred. Conclusion(s) Blastocyst-stage FET was associated with a lower ectopic/heterotopic pregnancy rate compared with cleavage-stage FET.

Objectives To examine the risks of neonatal and infant mortality in relation to infertility treatment and to quantify the extent to which preterm delivery mediates this relationship. Design Cross-sectional study. Setting United States, 2015–2018. Patient(s) A total of 14,961,207 pregnancies resulting in a singleton live birth. Intervention(s) Any infertility treatment, including assisted reproductive technology and fertility-enhancing drugs. Main Outcome Measure(s) Neonatal ( Result(s) Any infertility treatment was documented in 1.3% (n = 198,986) of pregnancies. Infertility treatment was associated with a 51% increased risk of neonatal mortality (RR 1.51, 95% CI 1.39–1.64), with a slightly higher risk for early neonatal mortality (RR 1.57, 95% CI 1.43–1.73) than late neonatal mortality (RR 1.33, 95% CI 1.11–1.58). These risks were similar for pregnancies conceived through assisted reproductive technology and fertility-enhancing drugs. The mediation analysis showed that 72% (95% CI 59–85) of the total effect of infertility treatment on neonatal mortality was mediated through preterm delivery. In a sensitivity analysis, following corrections for exposure misclassification and unmeasured confounding biases, these risks were higher for early, but not for late, neonatal mortality. Conclusion(s) Pregnancies conceived with infertility treatment are associated with increased neonatal mortality, and this association is largely mediated through preterm delivery. However, given the substantial underreporting of infertility treatment, these associations must be cautiously interpreted.

Objective To compare in vitro fertilization (IVF) outcomes in couples in which at least one partner is human immunodeficiency virus (HIV) positive with that of couples in which neither partner is HIV-positive. Design Retrospective matched case-control study. Setting Fertility center at Tenon Hospital, Paris, France. Patient(s) A total of 179 IVF cycles in couples infected with HIV-1 and 179 IVF cycles in control couples. Intervention(s) Ovarian stimulation, oocytes retrieval, IVF (standard and microinjection), embryo transfer, pregnancy, and live birth follow-up. Main Outcome Measure(s) Live birth rate and IVF outcomes Result(s) The first comparison between HIV and non-HIV couples showed poorer outcomes in the HIV group (higher administered gonadotropin doses and longer stimulation periods, lower cumulative pregnancy and live birth rates, among other things). A subgroup analysis was performed in addition. No differences were found in the “men HIV” group compared with the controls. In contrast, poorer outcomes in the “women HIV” and “women and men HIV” groups were shown in terms of administered doses, duration of stimulation, and number of oocytes retrieved. For the “women HIV” group, lower cumulative clinical pregnancy and live birth rates were found. Conclusion The data suggested that couples with HIV-positive women have poorer medically assisted procreation outcomes than couples with non-HIV-infected women. Therefore, physicians should pay particular attention to couples with HIV-positive women.

Resumen: Introducción: En torno al 0,2-6,1% de los recién nacidos en los países desarrollados han sido concebidos por técnicas de reproducción asistida (TRA). Se han descrito tasas más altas de malformaciones congénitas (MC) mayores y menores en esta población, pero los múltiples posibles factores de confusión asociados hacen difícil establecer una relación de causalidad directa con estos procedimientos y conocer los factores específicos implicados. Material y método: Se realizó un estudio prospectivo de cohorte controlado con el objetivo de determinar el riesgo de MC en niños-TRA. Se recogieron los datos específicos de la TRA de una cohorte de gestaciones clínicas de mujeres tratadas en la Unidad de Reproducción de un hospital público de tercer nivel durante dos años; 231 de 267 (87%) niños nacidos de dichas gestaciones-TRA participaron en el estudio y fueron valorados por un pediatra con formación en Genética Clínica y Dismorfología a los 12-20 y a los 26-40 meses de edad. De forma simultánea se seleccionó una cohorte de niños concebidos de forma natural (CN), de acuerdo con los criterios: siguiente recién nacido al caso del mismo grupo de edad materna, edad gestacional y tipo de gestación (única o múltiple); 230 niños CN fueron seleccionados y 208 (90%) participaron en el estudio. Resultados: Se detectaron MC mayores en el 7,8% de casos y en el 7,2% de controles, sin existir diferencias estadísticamente significativas entre ellos. Sí se identificaron diferencias en algunas malformaciones menores como las malformaciones capilares y lesiones pigmentarias, más frecuentes en el grupo TRA. Además, se identificó de forma inesperada un patrón craneofacial recurrente en el grupo TRA. Conclusiones: A pesar de las altas tasas de MC mayores, no se detectaron diferencias significativas entre grupos, pero sí entre algunas anomalías menores, lo que sugiere que las TRA tienen un impacto leve sobre el desarrollo embrionario. El fenotipo facial identificado no ha sido descrito previamente, así como el mayor riesgo de lesiones pigmentarias y malformaciones capilares. Son necesarios más estudios que corroboren estas asociaciones. Abstract: Introduction: About 0.2–6.1% of newborns in the developed world have been conceived by assisted reproductive techniques (ART). Higher rate of major and minor malformations have been described in this population, but the multiple possible confounders associated, make it difficult to establish a direct causal relationship, and the specific factors involved. Material and methods: To determine the risk of these malformations in our population, a collaborative prospective controlled cohort study was designed. We collected the specific ART-data related to the clinical gestation of women treated in a period of 2 years in the Reproduction Unit from a Spanish public tertiary-level hospital. 231 out of 267 newborns of these gestation (88%) were exhausted assessed by a Clinical Geneticist expertise in Dysmorphology at 12–20 and 26–40 months of age. At the same time a controlled group of children naturally conceived (NC) was selected according to the following criteria: the next NC newborn belonging to the same group of maternal and gestational age, and type of gestation (single or multiple). 230 controls were chosen and 208 participated in the study (90%). Results: Major malformations were presented in 7.8% of the ART-children and 7.2% of the controls, without founding statistically differences between groups. However, differences were found in the risk of some minor malformations such as capillary malformations and pigmentary lesions, higher in the ART-group. A recurrent pattern of craneofacial anomalies was also unexpectedly detected. Conclusions: In spite of the high rate of major congenital malformations detected, there were no differences between groups. Thus, our results suggest that ART may affect the normal embryonic development but in a milder way than other confounding factors do. The facial phenotype identified has not previously, either the higher risk of capillary malformations and pigmentary lesions. More studies are needed to confirm this association.

A genetic etiology of male infertility is identified in fewer than 25% of infertile men, while 30% of infertile men lack a clear etiology, resulting in a diagnosis of idiopathic male infertility. Advances in reproductive genetics have provided insights into the mechanisms of male infertility, and a characterization of the genetic basis of male infertility may have broad implications for understanding the causes of infertility and determining the prognosis, optimal treatment, and management of couples. In a substantial proportion of patients with azoospermia, known genetic factors contribute to male infertility. Additionally, the number of identified genetic anomalies in other etiologies of male infertility is growing through advances in whole-genome amplification and next-generation sequencing. In this review, we present an up-to-date overview of the indications for appropriate genetic tests, summarize the characteristics of chromosomal and genetic diseases, and discuss the treatment of couples with genetic infertility by microdissection-testicular sperm extraction, personalized hormone therapy, and in vitro fertilization with pre-implantation genetic testing.

STUDY QUESTION Does in vitro maturation (IVM) result in non-inferior cumulative live birth rates compared to those after standard in vitro fertilization (IVF) in infertile women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER One cycle of IVM, without any stimulation, was inferior to one cycle of standard IVF in women with PCOS in terms of 6-month cumulative live birth rates, when choosing single vitrified-warmed blastocyst transfer. WHAT IS KNOWN ALREADY IVM is an emerging alternative treatment for women with PCOS who need assisted reproductive technology. Since a minimal or even zero dose of gonadotropins are required in the IVM procedure, the occurrence of ovarian hyperstimulation syndrome (OHSS) is eliminated. Only one clinical trial comparing the pregnancy outcome between IVM with FSH priming and IVF has been reported. However, it is still unknown whether IVM treatment without any stimulation can offer a similar live birth outcome in women with PCOS as compared to that in women receiving the standard IVF procedure with ovarian stimulation. STUDY DESIGN, SIZE, DURATION This single-centre, open-label randomized controlled non-inferiority trial in an academic infertility centre in China was performed between March 2018 and July 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged 20–38 years with PCOS and infertility scheduled for their first IVF attempt were eligible. In total, 351 women were randomly allocated to receive one cycle of unstimulated IVM (n = 175) or one cycle of standard IVF with a flexible GnRH antagonist protocol and hCG as ovulatory trigger (n = 176). A freeze-all and single blastocyst transfer strategy was used in both groups. The primary outcome was ongoing pregnancy (leading to live birth) within 6 months after randomization. A non-inferiority margin of 15% was considered. MAIN RESULTS AND THE ROLE OF CHANCE The IVM procedure without additional gonadotropin resulted in a lower ongoing pregnancy (leading to live birth) within 6 months after randomization compared to standard IVF treatment (22.3% vs. 50.6%; rate difference −28.3%; 95% confidence interval [CI]: −37.9% to −18.7%). Moderate-severe OHSS did not occur in the IVM group, while in the IVF group, ten women (5.7%) had moderate OHSS and one woman (0.6%) had severe OHSS. There was no statistically significant difference in the occurrence of obstetric and perinatal complications. LIMITATIONS, REASONS FOR CAUTION The trial was conducted using an IVM protocol without additional stimulation in a single centre, which may limit its generalizability. In addition, a GnRH agonist trigger rather than hCG for IVF stimulation in women with PCOS would be more consistent with current clinical practice. WIDER IMPLICATIONS OF THE FINDINGS Although IVM is considered to be a convenient, inexpensive and safe alternative to IVF for women with PCOS, our results indicated that one cycle of IVM without any stimulation was inferior to one cycle of standard IVF in terms of the cumulative live birth rate. The inferiority of IVM without ovarian stimulation could be mainly due to the limitations in the developmental potential of embryos. Further IVM development should be tested and validated in a freeze-only and blastocyst transfer setting. Further RCTs are needed to evaluate the effectiveness and safety of other IVM protocols or multiple cycles of IVM compared to IVF. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China (2016YFC1000201 and 2018YFC1002104) and the National Science Foundation of China (81730038). B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). All other authors declare no competing interests. TRIAL REGISTRATION NUMBER Clinicaltrials.gov NCT03463772. TRIAL REGISTRATION DATE 29 January 2018. DATE OF FIRST PATIENT’S ENROLMENT 16 March 2018.

Although the incidence of the various gynecological cancers has been increasing in recent years, long-term survival is now possible for many patients thanks to advances in multimodality treatment. When treating gynecological cancer in adolescent and young adult (AYA) patients who desire future pregnancy, it is necessary to preserve the reproductive organs and their function to prevent loss of fertility. However, because treatment targets these organs, in the large majority of cases, patients must have these organs removed. In the subfield of oncofertility, treatment of the underlying disease takes priority, and the main principle is preventing delay in treatment. Close cooperation between obstetricians and gynecologists involved in reproductive medicine and oncologists involved in cancer treatment is necessary. In addition, it is important that clinicians work closely not only with other specialists but also with such medical professionals as nurses and counselors so that cancer patients of the AYA generation can be provided the support they need to fight their cancer with hope. Herein, we describe the current status of fertility-sparing therapy for AYA patients with gynecological cancer (cervical cancer, endometrial cancer, or ovarian cancer). In addition, we explain points to keep in mind during a patient's pregnancy after fertility preservation, the latest findings on assisted reproductive technology, and the challenges and prospects of fertility preservation therapy for patients with gynecologic cancer.

STUDY QUESTIONAre relative mitochondrial DNA (mtDNA) content and mitochondrial genome (mtGenome) variants in human cumulus cells (CCs) associated with oocyte reproductive potential and assisted reproductive technology (ART) outcomes?SUMMARY ANSWERNeither the CC mtDNA quantity nor the presence of specific mtDNA genetic variants was associated with ART outcomes, although associations with patient body mass index (BMI) were detected, and the total number of oocytes retrieved differed between major mitochondrial haplogroups.WHAT IS KNOWN ALREADYCCs fulfil a vital role in the support of oocyte developmental competence. As with other cell types, appropriate cellular function is likely to rely upon adequate energy production, which in turn depends on the quantity and genetic competence of the mitochondria. mtDNA mutations can be inherited or they can accumulate in somatic cells over time, potentially contributing to aging. Such mutations may be homoplasmic (affecting all mtDNA in a cell) or they may display varying levels of heteroplasmy (affecting a proportion of the mtDNA). Currently, little is known concerning variation in CC mitochondrial genetics and how this might influence the reproductive potential of the associated oocyte.STUDY DESIGN, SIZE, DURATIONThis was a prospective observational study involving human CCs collected with 541 oocytes from 177 IVF patients. mtDNA quantity was measured in all the samples with a validated quantitative PCR method and the entire mtGenome was sequenced in a subset of 138 samples using a high-depth massively parallel sequencing approach. Associations between relative mtDNA quantity and mtGenome variants in CCs and patient age, BMI (kg/m2), infertility diagnosis and ART outcomes were investigated.PARTICIPANTS/MATERIALS, SETTING, METHODSMassively parallel sequencing permitted not only the accurate detection of mutations but also the precise quantification of levels of mutations in cases of heteroplasmy. Sequence variants in the mtDNA were evaluated using Mitomaster and HmtVar to predict their potential impact.MAIN RESULTS AND THE ROLE OF CHANCEThe relative mtDNA CC content was significantly associated with BMI. No significant associations were observed between CC mtDNA quantity and patient age, female infertility diagnosis or any ART outcome variable. mtGenome sequencing revealed 4181 genetic variants with respect to a reference genome. The COXI locus contained the least number of coding sequence variants, whereas ATPase8 had the most. The number of variants predicted to affect the ATP production differed significantly between mitochondrial macrohaplogroups. The total number of retrieved oocytes was different between the H-V and J-T as well as the U-K and J-T macrohaplogroups. There was a non-significant increase in mtDNA levels in CCs with heteroplasmic mitochondrial mutations.LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONAlthough a large number of samples were analysed in this study, it was not possible to analyse all the CCs from every patient. Also, the results obtained with respect to specific clinical outcomes and macrohaplogroups should be interpreted with caution due to the smaller sample sizes when subdividing the dataset.WIDER IMPLICATIONS OF THE FINDINGSThese findings suggest that the analysis of mtDNA in CCs is unlikely to provide an advantage in terms of improved embryo selection during assisted reproduction cycles. Nonetheless, our data raise interesting biological questions, particularly regarding the interplay of metabolism and BMI and the association of mtDNA haplogroup with oocyte yield in ovarian stimulation cycles.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by National Institutes of Health grant 5R01HD092550-02. D.J.N. and C.R. co-hold patent US20150346100A1 and D.J.N. holds US20170039415A1, both for metabolic imaging methods. D.W. receives support from the NIHR Oxford Biomedical Research Centre. The remaining authors have no conflicts of interest to declare.

Background: Despite the widespread use of assisted reproductive technology (ART), few studies analyse its impact on the total fertility rate (TFR). Furthermore, very little is known about how ART affects fertility at older reproductive ages and contributes to family size. Objective: We aim to quantify the contribution of ART to total and age-specific fertility rates and in relation to the transition to first and subsequent births in Australia. Methods: Using data from a comprehensive clinical registry of ART treatments, age-specific ART and non-ART fertility rates were calculated and used to decompose the change in the TFR between 2010 and 2017 into ART and non-ART components. Results: ART represented an increasing and relevant contribution to the TFR, corresponding to an impact of the order of 4% to 5% per annum, or approximately to 1 in 20 births. Increasing fertility rates at age 33 and above exerted a positive effect on the overall TFR, and they were almost entirely attributable to the increasing use of ART. Women resorted to ART especially to have a first child. Contribution: This is the first study to provide a detailed examination of the contribution of ART to age-specific fertility rates and in relation to parity transition. While most studies focus on the impact of ART on the overall TFR, the importance of ART for the recovery of births at older reproductive ages could be underestimated.

OBJECTIVE This study described the development and psychometric evaluation of the fertility reparation inventory, providing measures of manic and expiatory reparation as symbolic dynamics of restoring one's procreative and generative identity through Assisted Reproductive Technology (ART). METHODS Two cross-sectional studies were conducted on female patients undergoing ART (N = 150) and women from the general population (N = 250), respectively. Exploratory factor analysis and confirmatory factor analysis assessed construct validity and reliability. Pearson's bivariate correlations were used to provide convergent evidence of validity with omnipotence, perceived infertility-related stress, anxiety, depression, need for reparation, fear of punishment, and hope. RESULTS The results confirmed a two-factor solution of the 12-item instrument, with adequate fit, a very good internal consistency, and well-supported forms of convergent validity. CONCLUSION This study provides a meaningful psychodynamic contribution, in both theoretical and empirical terms, for the understanding of emotional dynamics and psychological issues underlying the demand for ART.

The main goal of assisted reproductive technology (ART) is to achieve a healthy singleton live birth after the transfer of one embryo. A major objective of IVF scientists has always been to use adequate criteria for selecting the embryo for transfer according to its implantation potential. Indeed, embryo quality is usually assessed by evaluating visual morphology, which relies on the removal of the embryo from the incubator and might include inter- and intra-evaluator variation among embryologists. Recently, an advancement in embryo culture has taken place with the introduction of a new type of incubator with an integrated time-lapse monitoring system, which enables embryologists to analyse the dynamic events of embryo development from fertilization to blastocyst formation. This novel practice is rapidly growing and has been used in many IVF centres worldwide. Therefore, the main aim of this review is to present the benefits of time-lapse monitoring in a modern embryology laboratory; in particular, we discuss blastocyst collapse and morphometric blastocyst assessment, and analyse their association with embryo viability and implantation potential. In addition, we highlight preliminary studies involving artificial intelligence and machine learning models as non-invasive markers of clinical pregnancy.

Worldwide, there has been a trend toward later motherhood. Concurrently, the incidence of subfertility has been on the rise, necessitating conception using assisted reproductive technologies (ARTs). These pregnancies are considered high risk due to fetal complications such as antepartum stillbirth and growth restriction and maternal complications such as increase in maternal morbidity and mortality. Early induction of labor can help to mitigate these risks. However, this has to be balanced against the iatrogenic harms of earlier delivery to both the baby, including respiratory distress and NICU stay, and the mother who might experience longer labor and other complications such as uterine hyperstimulation. Induction of labor at 39 weeks is the optimal timing for preventing antepartum stillbirth and avoiding iatrogenic harm. Delivery by elective cesarean section is not advocated as its benefits in these patients are unclear compared with the short- and long-term complications of a major abdominal surgery.

Placenta accreta spectrum (PAS) refers to the range of pathologic adherence of the placenta to the uterine myometrium, including the placenta accreta, increta, and percreta. The incidence of PAS is rising primarily because of an increase in related risk factors, such as the rate of cesarean deliveries and pregnancies resulting from assisted reproductive technology. The maternal risks associated with PAS are significant, including hemorrhage, hysterectomy, and death. Fetal and neonatal risks are primarily the result of premature delivery. Antenatal diagnosis via ultrasonography and magnetic resonance imaging remains imperfect. Management of PAS varies, however, and there is a clear improvement in maternal outcomes with an antenatal diagnosis compared with unexpected diagnosis at the time of delivery. Studies that evaluate the balance between maternal and fetal/neonatal risks of expectant management versus preterm delivery have found that planned delivery between 34 and 35 weeks’ gestation optimizes outcomes. Multidisciplinary PAS care teams have become the norm and recommended approach to management, given the complexity of caring for this obstetrical condition. Although significant advances have been made over the years, large knowledge gaps remain in understanding the pathophysiology, diagnosis, and clinical management.

Assisted reproductive technology (ART) has become common amongst couples with infertility issues. ART is known to be successful, but epidemiological data indicates that ART is associated with placental disorders. Additionally, reports show increased risks of short- and long-term complications in children born to mothers undergoing ART. However, the mechanisms responsible for these events are obscure. The placenta is considered as a key organ for programming of diseases and ART procedures are suggested to alter the placental function and intrauterine growth trajectories. Epigenetic changes in maternal and foetal tissues are suggested to be the underlying mechanisms for these outcomes. Epigenetic regulation is known to evolve following fertilisation and before implantation and subsequently across gestation. During these critical periods of epigenetic 'programming', DNA methylation and chromatin remodelling influence the placental structure and function by regulating the expression of various genes. ART treatment coinciding with epigenetic 'programming' events during gametogenesis and early embryo development may alter the programming phases leading to long-term consequences. Thus, disruptions in placental development observed in ART pregnancies could be associated with altered epigenetic regulation of vital genes in the placenta. The review summarises available literature on the influence of ART procedures on epigenetic changes in the placenta.

Anti-Mullerian hormone (AMH) is secreted by ovarian granulosa cells and has become a surrogate marker for ovarian reserve. We review anticipated AMH levels throughout the reproductive lifespan and how AMH levels can be used in assisted reproductive technology. While AMH is a surrogate marker for ovarian reserve, values do not predict fertility. Patients with low versus normal AMH have similar fertility. AMH levels are helpful in guiding treatment for infertility, including medication dosing for IVF and anticipated cycle outcomes. AMH levels are positively correlated with ovarian response in IVF cycles. For cancer patients with planned gonadotoxic chemotherapy, AMH levels are useful in counseling patients prior to treatment, recommending fertility preservation options, and monitoring ovarian function following treatment. New studies have shown a possible protective effect of AMH injection on the ovaries for women undergoing gonadotoxic chemotherapy treatment. AMH levels are a useful adjunct to follicle-stimulating hormone (FSH) levels when diagnosing menopause and premature ovarian insufficiency (POI) and can be used to estimate the menopausal transition in women above the age of 40 but have limited clinical utility in predicting menopause for women at risk for POI. AMH is a useful tool to assess ovarian reserve and response to ovarian stimulation, but levels are not correlated with rates of conception and should not be used to counsel on spontaneous fertility. While AMH can be used as a quantitative measure of ovarian reserve, AMH level is not a qualitative marker for oocytes. AMH injection may be a therapeutic option for fertility preservation in the future.