Living in a low socioeconomic status neighbourhood is associated with lower cumulative ongoing pregnancy rate after IVF treatment

Research question: Does an association exist between neighbourhood socioeconomic status (SES) and the cumulative rate of ongoing pregnancies after 2.5 years of IVF treatment? Design: A retrospective observational study involving 2669 couples who underwent IVF or IVF and intracytoplasmic sperm injection treatment between 2006 and 2020. Neighbourhood SES for each couple was determined based on their residential postal code. Subsequently, SES was categorized into low (&lt;p20), medium (p20–p80), and high (&gt;p80). Multivariable binary logistic regression analyses were conducted, with the cumulative ongoing pregnancy within 2.5 years as the outcome variable. The SES category (reference category: high), female age (reference category: 32–36 years), body mass index (reference category: 23–25 kg/m2), smoking status (yes/no), number of oocytes after the first ovarian stimulation, embryos usable for transfer or cryopreservation after the first cycle, duration of subfertility before treatment and insemination type were used as covariates. Results: A variation in ongoing pregnancy rates was observed among SES groups after the first fresh embryo transfer. No difference was found in the median number of IVF treatment cycles carried out. The cumulative ongoing pregnancy rates differed significantly between SES groups (low: 44%; medium: 51%; high: 56%; P &lt; 0.001). Low neighbourhood SES was associated with significantly lower odds for achieving an ongoing pregnancy within 2.5 years (OR 0.66, 95% CI 0.52 to 0.84, P &lt; 0.001). Conclusion: Low neighbourhood SES compared with high neighbourhood SES is associated with reducing odds of achieving an ongoing pregnancy within 2.5 years of IVF treatment.</p

Living in a low socioeconomic status neighbourhood is associated with lower cumulative ongoing pregnancy rate after IVF treatment

Research question: Does an association exist between neighbourhood socioeconomic status (SES) and the cumulative rate of ongoing pregnancies after 2.5 years of IVF treatment? Design: A retrospective observational study involving 2669 couples who underwent IVF or IVF and intracytoplasmic sperm injection treatment between 2006 and 2020. Neighbourhood SES for each couple was determined based on their residential postal code. Subsequently, SES was categorized into low (&lt;p20), medium (p20–p80), and high (&gt;p80). Multivariable binary logistic regression analyses were conducted, with the cumulative ongoing pregnancy within 2.5 years as the outcome variable. The SES category (reference category: high), female age (reference category: 32–36 years), body mass index (reference category: 23–25 kg/m2), smoking status (yes/no), number of oocytes after the first ovarian stimulation, embryos usable for transfer or cryopreservation after the first cycle, duration of subfertility before treatment and insemination type were used as covariates. Results: A variation in ongoing pregnancy rates was observed among SES groups after the first fresh embryo transfer. No difference was found in the median number of IVF treatment cycles carried out. The cumulative ongoing pregnancy rates differed significantly between SES groups (low: 44%; medium: 51%; high: 56%; P &lt; 0.001). Low neighbourhood SES was associated with significantly lower odds for achieving an ongoing pregnancy within 2.5 years (OR 0.66, 95% CI 0.52 to 0.84, P &lt; 0.001). Conclusion: Low neighbourhood SES compared with high neighbourhood SES is associated with reducing odds of achieving an ongoing pregnancy within 2.5 years of IVF treatment.</p

Bone morphogenetic proteins and the polycystic ovary syndrome

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is defined by two out of the following three criteria being met: oligo- or anovulation, hyperandrogenism, and polycystic ovaries. Affected women are often obese and insulin resistant. Although the etiology is still unknown, members of the Transforming Growth Factor β (TGFβ) family, including Bone Morphogenetic Proteins (BMPs) and anti-Müllerian hormone (AMH), have been implicated to play a role. In this pilot study we aimed to measure serum BMP levels in PCOS patients. METHODS: Twenty patients, fulfilling the definition of PCOS according to the Rotterdam Criteria, were randomly selected. Serum BMP2, -4, -6 and −7 levels were measured using commercially available BMP2, BMP4, BMP6 and BMP7 immunoassays. RESULTS: Serum BMP2, serum BMP4 and serum BMP6 levels were undetectable. Three patients had detectable serum BMP7 levels, albeit at the lower limit of the standard curve. CONCLUSIONS: BMP levels were undetectable in almost all patients. This suggests that with the current sensitivity of the BMP assays, measurement of serum BMP levels is not suitable as a diagnostic tool for PCOS

Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further ∼2,000 clinically validated cases and ∼100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 × 10(-8)), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P=2.5 × 10(-9)), higher insulin resistance (P=6 × 10(-4)) and lower serum sex hormone binding globulin concentrations (P=5 × 10(-4)). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P=1.6 × 10(-8)) and PCOS-susceptibility alleles are associated with higher serum anti-Müllerian hormone concentrations in girls (P=8.9 × 10(-5)). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk.This work was supported by the Medical Research Council [U106179472; MC_U106179472; U106179471; MC_U106179471] and the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981 to 23andMe). The UK Medical Research Council and Wellcome Trust (092731), together with the University of Bristol, provide core support for the ALSPAC study. AMH assays in ALSPAC were funded with a grant from the US National Institute of Health (R01 DK077659). DAL works in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_12013/5).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms946

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

Contains fulltext : 109739.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. METHODS/DESIGN: Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. DISCUSSION: The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. TRIAL REGISTRATION: NTR2657

Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown

Early initiation of gonadotropin-releasing hormone antagonist treatment results in a more stable endocrine milieu during the mid- and late-follicular phases: a randomized controlled trial comparing gonadotropin-releasing hormone antagonist initiation on cycle day 2 or 6

Objective: to compare the effect of initiating GnRH antagonist (GnRH-a) on cycle day (CD) 2 vs. CD 6 on LH, E2, and P levels in the mid and late follicular phases.Design: nested study within a multicenter randomized controlled trial.Setting: reproductive medicine center in an university hospital.Patient(s): one hundred sixty patients undergoing IVF/intracytoplasmic sperm injection (ICSI).Intervention(s): recombinant FSH (150–225 IU) was administered daily from CD 2 onward. The study group (CD 2) started GnRH-a cotreatment on CD 2, whereas the control group (CD 6) started on CD 6.Main Outcome Measure(s): the follicular phase endocrine profile.Result(s): the LH levels on CD 6 were lower in the CD 2 group (0.6 ± 0.4 vs. 1.9 ± 1.4 IU/L). The CD 2 group demonstrated both lower E2 levels on CD 6 (520.1 ± 429.6 pmol/L vs. 1,071.7 ± 654.2 pmol/L) and on the day of hCG administration (3,341.4 ± 1,535.3 pmol/L vs. 4,573.2 ± 2,445.4 pmol/L). The P levels did not differ on CD 6 or on the day of hCG administration.Conclusion(s): early initiation of GnRH-a cotreatment results in a more stable endocrine profile, with more physiological levels of E2 and LH during the follicular phase. The effect on clinical outcomes must be established in larger trial

Impact of an mHealth Platform for Pregnancy on Nutrition and Lifestyle of the Reproductive Population: A Survey

BACKGROUND: Poor nutrition and lifestyle behaviors exert detrimental effects on reproduction and health during the life course. Therefore, lifestyle interventions during the periconceptional period can improve fertility, pregnancy outcome, and health of subsequent generations. OBJECTIVE: This survey investigates the compliance, usability, and initial effectiveness of the Web-based mHealth platform, Smarter Pregnancy. METHODS: A free subscription to the mHealth platform, Smarter Pregnancy, was provided to couples contemplating pregnancy (n=1275) or already pregnant (n=603). After baseline identification of inadequate nutrition and lifestyle behaviors, a personal online coaching program of 6 months was generated. Using multiple imputation and the generalized estimating equation model with independent correlations, we estimated the changes from inadequate to adequate nutrition and lifestyle behaviors over time. Subgroup analyses were performed for (1) overweight and obese women (body mass index [BMI] ≥25 kg/m(2)), (2) pregnant women at the start of the program, and (3) couples. RESULTS: A 64.86% (1218/1878) compliance rate was observed and 54.7% (range 39.2-73.4%) of participants rated the program usability as positive or very positive. Adequate nutrition and lifestyle behaviors at baseline were 21.57% (405/1878) for vegetable intake, 52.61% (988/1878) for fruit intake, 85.44% (1303/1525) for folic acid use, 86.79% (1630/1878) for no tobacco use, and 64.43% (1210/1878) for no alcohol consumption. After 6 months of coaching, these lifestyle behaviors improved by 26.3% (95% CI 23.0-29.9) for vegetable intake, 38.4% (95% CI 34.5-42.5) for fruit intake, 56.3% (95% CI 48.8-63.6) for folic acid use, 35.1% (95% CI 29.1-41.6) for no tobacco use, and 41.9% (95% CI 35.2-48.9) for no alcohol consumption. The program showed the strongest effectiveness for participating couples. CONCLUSIONS: This novel Web-based mHealth platform shows high compliance and usability, and users demonstrate improvements in nutrition and lifestyle behaviors. The next step will be further validation in randomized controlled trials and implementation