Impact of COVID-19 on Infertility Treatments: Not Even A Global Pandemic Was Strong Enough to Hamper Successful Pregnancies

The COVID-19 global pandemic has meant a sanitary and social threat at every level and it was not any different for the assisted reproduction industry. This retrospective two-arm study aims to describe its impact on infertility treatments performed in our clinics (IVI Spain, Rome, and Lisbon) regarding: (1) assessment of COVID-19 impact in the amount, type, and success of infertility treatments performed during 2020 compared to 2019; and (2) description of the psychological status of women who got pregnant during the first months of the pandemic and its correlation with their final pregnancy outcome. On the one hand, this pandemic has led to a significant reduction in the total number of treatments performed, even though the proportion of the different types was almost unaltered. Additionally, its impact on pregnancy rates was not clinically relevant. On the other hand, the psychological status of pregnant women did not seem to affect their final pregnancy outcome. These results suggest that, even in the event of a negatively affected psychological status in our study population, it was not translated into an impaired pregnancy outcome. Hence, the COVID-19 global pandemic, although devastating, might not have exerted a clinically relevant negative impact on the overall pregnancy outcome in our clinics.

Sildenafil Supplementation for Women Undergoing Infertility Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The aim of this systematic review and meta-analysis is to summarize data on the effectiveness of Sildenafil supplementation for women undergoing assisted reproduction techniques. This meta-analysis of randomized controlled trials (RCTs) evaluates the effects of Sildenafil administration during infertility treatments compared with a control group in infertile women. Outcomes evaluated were endometrial thickness (ETh) and the clinical pregnancy rate (CPR). The chemical pregnancy rate (ChPR) was also evaluated. Pooled results were expressed as the risk ratio (RR) or mean differences (MD) with a 95% confidence interval (95% CI). Women undergoing ovulation induction who received Sildenafil showed higher ETh and a higher CPR in comparison to controls. In this group, both the ETh and ChPR resulted in significantly higher values only with delayed start administration. Women undergoing fresh or frozen embryo transfer who received Sildenafil showed no significant advantages regarding ETh and CPR in comparison to controls. In this group, we found a significantly higher ChPR in women receiving Sildenafil. A subgroup analysis revealed significant advantages regarding ETh with oral administration for women undergoing fresh or frozen embryo transfer. Sildenafil therapy appears to improve endometrial thickness and pregnancy rate in women undergoing timed intercourses but it resulted not effective in IUI and IVF treatments. Further RCTs with rigorous methodology are still mandatory.

577Inequalities in access to in vitro fertilisation treatment in France

Background In vitro fertilisation (IVF) treatment is one of the most expensive infertility treatments. Cost has been described as a substantial barrier to access. In France all infertility treatments, including IVF, are fully reimbursed, but are there other barriers to access? Methods Based on the French national health insurance database that exhaustively records reimbursed healthcare, this cohort study included all women aged 18–49 years unsuccessfully treated with ovarian induction (first-line infertility treatment) between January–August 2016. Outcome was IVF access within 24 months of starting first-line treatment. Univariate and multivariate regressions explored age, disadvantaged social status, driving time to nearest IVF centre, and deprivation index of area of residence. Results Over 20,000 women unsuccessfully received first-line treatment. Almost 80% did not access IVF within 24 months. After age 34, probability of access decreased. Disadvantaged social status and living in a disadvantaged area were associated with lower probability of accessing IVF. Driving time to the nearest IVF centre was not significantly associated with access. Conclusions Socio-economic barriers to access IVF exist despite full treatment reimbursement in France. To reduce health inequalities, we need to better understand the nature and patterns of these barriers among less socially advantaged people. Key messages After failure of first-line infertility treatment, only 20% of women access IVF although it is fully reimbursed in France. Age, but most importantly socio-economic status, is a key determinant of access to IVF treatment. Distance from nearest IVF centre does not appear significant in explaining access to treatment in France.

The complex relationship between infertility and female genital tract cancer: A review

Introduction: The link between female infertility and gynecological cancer has always been a debated and challenging topic. Although cervical cancer has the worst impact on female fertility, as it is usually diagnosed in patients of reproductive age, endometrial and ovarian cancer are also diagnosed and treated often in relatively younger patients in which fertility preservation is a relevant issue. The aim of this review is to highlight the correlation between therapy for female infertility and the developing cancer’s risk and to describe the fertility sparing treatments in gynecological oncology. Material and methods: A systematic review of the literature through the main scientific search engines (PubMed and Google Scholar) was performed. We selected the most relevant articles based on the largest case series and the latest updates. All selected documents have been listed in the references. Results: Fifty-six relevant articles published between 1996 and 2019 were identified. Results from the available evidence report no significant increased risk of endometrial, cervical, and ovarian cancer in patients having infertility treatments. In young patients diagnosed with gynecological cancer, preservation of fertility is a personalized choice depending on several factors (type, stage, age and desire to conceive, safety of the treatment, and feasibility of fertility sparing surgery). For ovarian cancer FIGO stage IA G1, IA G2 (grade), and IC G1; for endometrial adenocarcinoma grade 1 with no lymphovascular space invasion (LVSI) or myometrial invasion and for early-stage cervical cancer (FIGO stage 2018: IA1-IB1), fertility sparing treatment is possible. The role of fertility sparing treatment with the increase of personalization of therapies therapy is always a theme of discussion and research. Conclusion: At present data regarding the risk of gynecological cancers after infertility treatments are reassuring. Careful evaluation of female fertility-sparing options in young women interested by ovarian, endometrial, or cervical tumors should be carried out involving a multidisciplinary team and ensuring safety and efficacy.

Challenges affecting couples resorting to Assisted Reproductive Treatment (ART) in Romania

Objective: The aim of this paper is to illustrate the main points of interest regarding the way treatment of infertility impacts the life of couples who struggle with this condition in Romania. The unique aspects and specific challenges regarding social, financial and psychological implications that affect Romanian couples who access specialized treatment for infertility will be thoroughly discussed. Methods: This study is a descriptive cross-sectional research. The sample population included patients who attended specialized infertility treatment (Assisted Reproductive Techniques - ART) in Fertility Clinics from Romania. The study was conducted between 2017 and 2019 and data was gathered through two infertility questionnaires. Results: The questionnaire for women was filled in by 829 female participants who struggled with infertility and resorted to ART and the questionnaire for men was completed by 227 male participants, as partners of the women, some of them as well with fertility issues. We analysed the results regarding all aspects surrounding infertility and ART, such as: psychological implications, impact of stress, access to specialized treatment, costs for treatment. Conclusion: The results showed that couples who struggle with infertility have to deal with high costs for specialized infertility treatments, in addition to stress related to treatment, creating a combination which negatively impacts their future chances of getting a pregnancy.

P–610 Optimal timing of ovulation triggering to achieve highest success rates in natural cycles – an analysis based on follicle size and estradiol concentration in NC-IVF

Study question What is the best follicle size, estradiol (E2) serum concentration and endometrial thickness to trigger ovulation in natural cycles? Summary answer Optimal follicles size is 18–22mm but estrogen concentration also need to be considered to maximize oocyte maturity and to minimize premature LH surge. What is known already Timing of the ovulation triggering is essential in infertility treatments based on natural menstrual cycles such as optimized vaginal intercourse, intrauterine inseminations and thawing cycles without hormone replacement therapy. Common parameters to define the day of ovulation triggering are the follicle size and the estrogen concentration. However, data on follicle size and estrogen concentration are either derived from longitudinal evaluations of few ideal participants, are not very detailed or were studied in stimulated cycles. The model of Natural Cycle IVF (NC-IVF) which provides more detailed information has never been used to study this issue. Study design, size, duration Retrospective cross sectional analysis of monofollicular NC-IVF cycles. Follicle size, E2 and LH serum concentrations and endometrial thickness were evaluated on day –5 to 0 (day 0 = day of aspiration). Ovulation was triggered with 5.000IE HCG 36h before aspiration if follicle size was 14–22mm. Patients with irregular cycles, endometriosis >II°, cycles with azoospermia or cryptozoospermia and with inconsistent data were excluded. 606 cycles from 290 women were analysed from 2016 to 2019. Participants/materials, setting, methods Mean age of women undergoing NC-IVF was 35.8±4.0y, median 36y [IQ-range: 34;39]. Each woman performed mean 2.1±1.4, median: 2 [IQ-range: 1–3] NC-IVF cycles at an university based IVF center. All parameters were analysed inter and intraindividually and associations were adjusted for maturity of oocyte, zygote development rate, embryo score, implantation rate and live birth rate. Associations were adjusted for age, cause of infertility and number of previous transfers. Main results and the role of chance Follicle size, E2 concentration and endometrial thickness increased constantly over time. The increase was computed for each cycle without considering any correlation intra patient, revealing an increase of follicle size by 1.04±0.64mm, an increase of E2 concentration by 167.3±76.8pmol/L and endometrial thickness by 0.69±0.59mm per day. Based on a multivariate adjusted model with follicle size, E2 and their interaction, number of retrieved oocytes was associated with E2 concentration (aOR 1.80, 95% CI 1.05–3.11; p = 0.034). Maturity of oocytes was associated not only with E2 concentration (aOR 1.84, 95% CI 1.15–2.94; p = 0.010) but also with follicle size (aOR 1.24, 95% CI 1.01–1.53; p = 0.037) and so was also the interaction of both parameters (aOR 0.96, 95% CI 0.94–0.99; p = 0.017). LH surge was calculated to start in 25% of cases at an E2 level of 545 pmol/l, in 50% of cases at 907pmol/l and in 75% of cases at an E2 level of 1531pmol/l. Live birth rate in cycles with follicles size 14–17 mm was 2.2–3.5% per initiated cycle and in cycles with follicle size 18–22mm 8.5–12.5%. Limitations, reasons for caution Cross sectional studies provides less precise information than longitudinal studies. Follicle size and endometrial thickness were evaluated by several physicians possibly causing some imprecision. Wider implications of the findings: There is a trend towards natural treatment cycles. The study contribute to an optimisation of infertility treatments involving natural cycles. The study gives guidance about the number of days required after a follicle monitoring to reach the optimal time for triggering ovulation. Trial registration number Not applicable

P–773 Infertility treatment and the risk of small for gestational age births: a population-based study in the United States

Study question What is the association between infertility treatments and small for gestational age (SGA) births? Summary answer Women who conceived pregnancies with any infertility treatment had a decreased risk of SGA <10th, <5th and <3rd percentiles compared to naturally conceived pregnancies. What is known already Assisted reproductive technology (ART) and other infertility treatments have long been associated with an increased risk of SGA births, which confers a greater risk of perinatal morbidity and mortality compared to appropriate for gestational age births. Study design, size, duration This is a cross-sectional study of 16,836,228 births in the United States (US) between 2015–2019. The exposure group included women who underwent any infertility treatment, including ART and prescribed fertility enhancing medications. The comparison group included those who had naturally conceived pregnancies. The primary outcome was SGA birth, defined as sex-specific birthweight <10th percentile for gestational age. Secondary outcomes included SGA <5th and <3rd percentile births. Participants/materials, setting, methods Pregnant subjects (n = 16,836,228) in the US who delivered non-malformed, singleton live births between 24–44 weeks’ gestational age. We estimated risk of SGA births in relation to any infertility treatment from fitting log-linear Poisson regression models with robust variance. Risk ratios (RR) and 95% confidence intervals (CI) were estimated as the effect measure before and after adjusting for confounders. We also performed a sensitivity analysis to correct for potential non-differential exposure misclassification and unmeasured confounding biases. Main results and the role of chance During the study period, 1.4% (n = 231,177) of non-malformed singleton live births resulted from infertility treatments (0.8% ART and 0.6% fertility enhancing medications). Of these, 9.4% (n = 21,771) of pregnancies conceived with infertility treatment were complicated by SGA <10th percentile compared to 11.9% (n = 1,755,925) of naturally conceived pregnancies. For pregnancies conceived with infertility treatment versus naturally conceived pregnancies, the adjusted RR for SGA <10th percentile was 1.07 (95% CI 1.06, 1.08). However, after correction for misclassification bias and unmeasured confounding, infertility treatment was found to be protective for SGA and conferred a 27% reduced risk of SGA <10th percentile (bias-corrected RR 0.73, 95% CI 0.53, 0.85). These trends were similar for analyses stratified by exposure to ART and fertility enhancing medications and secondary SGA outcomes, including SGA <5th and <3rd percentile. Limitations, reasons for caution All information collected on infertility treatment relies on self-reporting by patients and recording by hospital staff at the time of delivery, which likely resulted in underreporting of infertility treatments. Additionally, we cannot determine the impact of interventions that were not recorded, such as intrauterine insemination (IUI). Wider implications of the findings: Compared to naturally conceived pregnancies, exposure to infertility treatment is associated with reduction in the risk of SGA births. These findings, which are contrary to some published reports, likely reflect changes in the modern practice of infertility care in the US, and importantly, robust analysis of the national data. Trial registration number Not applicable