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 (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 < 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 < 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.

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome.

OBJECTIVES: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. DESIGN: A cross-sectional study. PARTICIPANTS: 200 women aged >45 with PCOS, and 200 age-matched controls. MEASUREMENTS: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. RESULTS: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P < .001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P < .001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. CONCLUSIONS: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning long-term risk for CVD.

Gonadotrophins versus clomifene citrate with or without intrauterine insemination in women with normogonadotropic anovulation and clomifene failure (M-OVIN): a randomised, two-by-two factorial trial.

BACKGROUND: In many countries, clomifene citrate is the treatment of first choice in women with normogonadotropic anovulation (ie, absent or irregular ovulation). If these women ovulate but do not conceive after several cycles with clomifene citrate, medication is usually switched to gonadotrophins, with or without intrauterine insemination. We aimed to assess whether switching to gonadotrophins is more effective than continuing clomifene citrate, and whether intrauterine insemination is more effective than intercourse. METHODS: In this two-by-two factorial multicentre randomised clinical trial, we recruited women aged 18 years and older with normogonadotropic anovulation not pregnant after six ovulatory cycles of clomifene citrate (maximum of 150 mg daily for 5 days) from 48 Dutch hospitals. Women were randomly assigned using a central password-protected internet-based randomisation programme to receive six cycles with gonadotrophins plus intrauterine insemination, six cycles with gonadotrophins plus intercourse, six cycles with clomifene citrate plus intrauterine insemination, or six cycles with clomifene citrate plus intercourse. Clomifene citrate dosages varied from 50 to 150 mg daily orally and gonadotrophin starting dose was 50 or 75 IU daily subcutaneously. The primary outcome was conception leading to livebirth within 8 months after randomisation defined as any baby born alive after a gestational age beyond 24 weeks. Primary analysis was by intention to treat. We made two comparisons, one in which gonadotrophins were compared with clomifene citrate and one in which intrauterine insemination was compared with intercourse. This completed study is registered with the Netherlands Trial Register, number NTR1449. FINDINGS: Between Dec 8, 2008, and Dec 16, 2015, we randomly assigned 666 women to gonadotrophins and intrauterine insemination (n=166), gonadotrophins and intercourse (n=165), clomifene citrate and intrauterine insemination (n=163), or clomifene citrate and intercourse (n=172). Women allocated to gonadotrophins had more livebirths than those allocated to clomifene citrate (167 [52%] of 327 women vs 138 [41%] of 334 women, relative risk [RR] 1·24 [95% CI 1·05-1·46]; p=0·0124). Addition of intrauterine insemination did not increase livebirths compared with intercourse (161 [49%] vs 144 [43%], RR 1·14 [95% CI 0·97-1·35]; p=0·1152). Multiple pregnancy rates for the two comparisons were low and not different. There were three adverse events: one child with congenital abnormalities and one stillbirth in two women treated with clomifene citrate, and one immature delivery due to cervical insufficiency in a woman treated with gonadotrophins. INTERPRETATION: In women with normogonadotropic anovulation and clomifene citrate failure, a switch of treatment to gonadotrophins increased the chance of livebirth over treatment with clomifene citrate; there was no evidence that addition of intrauterine insemination does so. FUNDING: The Netherlands Organization for Health Research and Development.

Sexual function in women with polycystic ovary syndrome: a systematic review and meta-analysis.

We present the first systematic review and meta-analysis of sexual function in women with polycystic ovary syndrome (PCOS) compared with women without PCOS. Data on this topic are limited and often contradicting. Sexual function is influenced by endocrine, mental and social factors, which are often compromised in women with PCOS. The main outcome measures were validated sexual function questionnaires and visual analogue scales (VAS). We identified and assessed 1925 original articles; 18 articles were included. Significant small effect sizes were found on sexual function subscales (total score: P = 0.006; arousal: P = 0.019; lubrication: P = 0.023; satisfaction: P = 0.015; orgasm: P = 0.028), indicating impaired sexual function in women with PCOS. Large effect sizes for the effect of body hair on sex were shown on VAS (P = 0.006); social effect of appearance (P = 0.007); sexual attractiveness (P < 0.001). Satisfaction with sex life was impaired (P < 0.001), but sexual satisfaction was rated equally important in women with PCOS and controls. We conclude that a satisfying sex life is important for women with PCOS; however, sexual function and feelings of sexual attractiveness are impaired. The findings imply that sexual function, sexual satisfaction and psychosocial functioning need to be part of every clinical assessment of women with PCOS.

Single-cell DNA sequencing reveals a high incidence of chromosomal abnormalities in human blastocysts.

Aneuploidy, a deviation from the normal chromosome copy number, is common in human embryos and is considered a primary cause of implantation failure and early pregnancy loss. Meiotic errors lead to uniformly abnormal karyotypes, while mitotic errors lead to chromosomal mosaicism: the presence of cells with at least 2 different karyotypes within an embryo. Knowledge about mosaicism in blastocysts mainly derives from bulk DNA sequencing (DNA-Seq) of multicellular trophectoderm (TE) and/or inner cell mass (ICM) samples. However, this can only detect an average net gain or loss of DNA above a detection threshold of 20%-30%. To accurately assess mosaicism, we separated the TE and ICM of 55 good-quality surplus blastocysts and successfully applied single-cell whole-genome sequencing (scKaryo-Seq) on 1,057 cells. Mosaicism involving numerical and structural chromosome abnormalities was detected in 82% of the embryos, in which most abnormalities affected less than 20% of the cells. Structural abnormalities, potentially caused by replication stress and DNA damage, were observed in 69% of the embryos. In conclusion, our findings indicated that mosaicism was prevalent in good-quality blastocysts, whereas these blastocysts would likely be identified as normal with current bulk DNA-Seq techniques used for preimplantation genetic testing for aneuploidy.

Mobile Health Coaching on Nutrition and Lifestyle Behaviors for Subfertile Couples Using the Smarter Pregnancy Program: Model-Based Cost-Effectiveness Analysis.

BACKGROUND: The health care costs for reproductive care have substantially increased with the use of in vitro fertilization (IVF) treatment. The mobile health (mHealth) coaching program Smarter Pregnancy is an effective intervention to improve nutrition and lifestyle behaviors and pregnancy rates in (sub)fertile couples, including those who undergo IVF treatment. Therefore, we hypothesize that this mHealth program can also reduce health care costs associated with IVF treatment. OBJECTIVE: This study aimed to evaluate the cost-effectiveness of the mHealth coaching program Smarter Pregnancy and compare it to usual care in women of subfertile couples who start their first IVF cycle. METHODS: This model-based cost-effectiveness analysis was performed on data from couples undergoing IVF treatment at the Erasmus MC, University Medical Center Rotterdam. A decision tree model was used to assess the incremental cost-effectiveness ratio (ICER) of ongoing pregnancies and costs of use of the mHealth program as compared to usual care. A probabilistic sensitivity analysis was performed to consider the uncertainty surrounding the point estimates of the input parameters. RESULTS: Based on our model including 793 subfertile women undergoing IVF treatment, use of the mHealth program resulted in 86 additional pregnancies and saved €270,000 compared to usual care after two IVF cycles, with an ICER of -€3050 (95% CI -3960 to -540) per additional pregnancy. The largest cost saving was caused by the avoided IVF treatment costs. Sensitivity analyses showed that the mHealth program needs to increase the ongoing pregnancy rate by at least 51% after two IVF cycles for cost saving. CONCLUSIONS: The mHealth coaching program Smarter Pregnancy is potentially cost saving for subfertile couples preceding their first IVF treatment. Implementation of this mHealth program in routine preconception care for subfertile couples should be seriously considered, given the relatively low costs and promising cost-effectiveness estimates.

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.

Cardiovascular risk management after reproductive and pregnancy-related disorders: A Dutch multidisciplinary evidence-based guideline.

BACKGROUND: In the past decades evidence has accumulated that women with reproductive and pregnancy-related disorders are at increased risk of developing cardiovascular disease (CVD) in the future. Up to now there is no standardised follow-up of these women becausee guidelines on cardiovascular risk management for this group are lacking. However, early identification of high-risk populations followed by prevention and treatment of CVD risk factors has the potential to reduce CVD incidence. Therefore, the Dutch Society of Obstetrics and Gynaecology initiated a multidisciplinary working group to develop a guideline for cardiovascular risk management after reproductive and pregnancy-related disorders. METHODS: The guideline addresses the cardiovascular risk consequences of gestational hypertension, preeclampsia, preterm delivery, small-for-gestational-age infant, recurrent miscarriage, polycystic ovary syndrome and premature ovarian insufficiency. The best available evidence on these topics was captured by systematic review. Recommendations for clinical practice were formulated based on the evidence and consensus of expert opinion. The Dutch societies of gynaecologists, cardiologists, vascular internists, radiologists and general practitioners reviewed the guideline to ensure support for implementation in clinical practice. RESULTS: For all reproductive and pregnancy-related disorders a moderate increased relative risk was found for overall CVD, except for preeclampsia (relative risk 2.15, 95% confidence interval 1.76-2.61). CONCLUSION: Based on the current available evidence, follow-up is only recommended for women with a history of preeclampsia. For all reproductive and pregnancy-related disorders optimisation of modifiable cardiovascular risk factors is recommended to reduce the risk of future CVD.

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 ß (TGFß) 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.