Obesity and Female Infertility: Potential Mediators of Obesity's Impact

BACKGROUND: Here we describe the consensus guideline methodology, summarise the evidence-based recommendations we provided to the World Health Organisation (WHO) for their consideration in the development of global guidance and present a narrative review on the management of anovulatory infertility in women with polycystic ovary syndrome (PCOS). OBJECTIVE AND RATIONALE: The aim of this paper was to present an evidence base for the management of anovulatory PCOS. SEARCH METHODS: The evidence to support providing recommendations involved a collaborative process for: (i) identification of priority questions and critical outcomes, (ii) retrieval of up-to-date evidence and exiting guidelines, (iii) assessment and synthesis of the evidence and (iv) the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation, the methodologist evaluated the quality of the supporting evidence that was then graded as very low, low, moderate or high for consideration during consensus. OUTCOMES: Evidence was synthesized and we made recommendations across the definition of PCOS including hyperandrogenism, menstrual cycle regulation and ovarian assessment. Metabolic features and the impact of ethnicity were covered. Management includes lifestyle changes, bariatric surgery, pharmacotherapy (including clomiphene citrate (CC), aromatase inhibitors, metformin and gonadotropins), as well as laparoscopic surgery. In-vitro fertilization (IVF) was considered as were the risks of ovulation induction and of pregnancy in PCOS. Approximately 80% of women who suffer from anovulatory infertility have PCOS. Lifestyle intervention is recommended first in women who are obese largely on the basis of general health benefits. Bariatric surgery can be considered where the body mass index (BMI) is ≥35 kg/m(2) and lifestyle therapy has failed. Carefully conducted and monitored pharmacological ovulation induction can achieve good cumulative pregnancy rates and multiple pregnancy rates can be minimized with adherence to recommended protocols. CC should be first-line pharmacotherapy for ovulation induction and letrozole can also be used as first-line therapy. Metformin alone has limited benefits in improving live birth rates. Gonadotropins and laparoscopic surgery can be used as second-line treatment. There is no clear evidence for efficacy of acupuncture or herbal mixtures in women with PCOS. For women with PCOS who fail lifestyle and ovulation induction therapy or have additional infertility factors, IVF can be used with the safer gonadotropin releasing hormone (GnRH) antagonist protocol. If a GnRH-agonist protocol is used, metformin as an adjunct may reduce the risk of ovarian hyperstimulation syndrome. Patients should be informed of the potential side effects of ovulation induction agents and of IVF on the foetus, and of the risks of multiple pregnancy. Increased risks for the mother during pregnancy and for the child, including the exacerbating impact of obesity on adverse outcomes, should also be discussed. WIDER IMPLICATIONS: This guidance generation and evidence-synthesis analysis has been conducted in a manner to be considered for global applicability for the safe administration of ovulation induction for anovulatory women with PCOS.

The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance

Whilst many multiparous women are obese (body mass index >30 kg/m(2)), obesity has been associated with impaired fecundity; however, the mechanism which links obesity to reduced fertility remains to be fully elucidated. Obese women, particularly those with central obesity, are less likely to conceive per cycle. Obese women suffer perturbations to the hypothalamic-pituitary-ovarian axis, menstrual cycle disturbance and are up to three times more likely to suffer oligo-/anovulation. A fine hormonal balance regulates follicular development and oocyte maturation, and it has been observed that obesity can alter the hormonal milieu. Leptin, a hormone produced by adipocytes, is elevated in obese women, and raised leptin has been associated with impaired fecundity. Obesity impairs ovulation but has also been observed to detrimentally affect endometrial development and implantation. The expression of polycystic ovary syndrome (PCOS) is regulated, in part, by weight, and so obese women with PCOS often have a more severe phenotype and experience more subfertility. Obesity also impairs the response of women to assisted conception treatments. Weight loss through lifestyle modification or bariatric surgery has been demonstrated to restore menstrual cyclicity and ovulation and improve the likelihood of conception. In this article, we will discuss the effect of obesity upon key reproductive mechanisms and its relation to fertility treatments.

/pdf/the-adverse-effects-of-obesity-on-conception-and-1i68nbv55n.pdf

The adverse effects of obesity on conception and implantation

Context Use of bariatric surgery has increased dramatically during the past 10 years, particularly among women of reproductive age. Objectives To estimate bariatric surgery rates among women aged 18 to 45 years and to assess the published literature on pregnancy outcomes and fertility after surgery. Evidence Acquisition Search of the Nationwide Inpatient Sample (1998-2005) and multiple electronic databases (Medline, EMBASE, Controlled Clinical Trials Register Database, and the Cochrane Database of Reviews of Effectiveness) to identify articles published between 1985 and February 2008 on bariatric surgery among women of reproductive age. Search terms included bariatric procedures, fertility, contraception, pregnancy, and nutritional deficiencies. Information was abstracted about study design, fertility, and nutritional, neonatal, and pregnancy outcomes after surgery. Evidence Synthesis Of 260 screened articles, 75 were included. Women aged 18 to 45 years accounted for 49% of all patients undergoing bariatric surgery (>50 000 cases annually for the 3 most recent years). Three matched cohort studies showed lower maternal complication rates after bariatric surgery than in obese women without bariatric surgery, or rates approaching those of nonobese controls. In 1 matched cohort study that compared maternal complication rates in women after laparoscopic adjustable gastric band surgery with obese women without surgery, rates of gestational diabetes (0% vs 22.1%, P  Conclusion Rates of many adverse maternal and neonatal outcomes may be lower in women who become pregnant after having had bariatric surgery compared with rates in pregnant women who are obese; however, further data are needed from rigorously designed studies.

https://jamanetwork.com/journals/jama/articlepdf/182893/jcr80003_2286_2296.pdf

Pregnancy and Fertility Following Bariatric Surgery: A Systematic Review

Background: Obesity and anovulation are common medical problems in the United States. Anovulation in obese patients primarily manifests with irregular, sporadic or absent menstrual bleeding. Weight loss of at least 5% has been shown to reverse obesity-related anovulation. The aim of this study was to assess the impact of bariatric surgery on infertility in morbidly obese women and to identify factors associated with return of normal menses following bariatric surgery. Methods: A survey of patients was collected from the bariatric surgery data-base at the Hospital of the University of Pennsylvania. 410 women under the age of 40 were sent questionnaires. 195 patients completed the questionnaire, and 29 patients had incorrect addresses without a forwarding address, resulting in a 51.2% response rate. Patients who reported menstrual cycle lengths >35 days were considered abnormal. 92 of the 195 responders were considered anovulatory preoperatively, based on menstrual history. Results: There was no significant difference in postoperative BMI, BMI decrease or age at surgery between the survey responders and non-responders. There was a significant difference between these 2 groups in time since surgery (P=.01). Both groups had a decrease in BMI of >18 kg/m2. The mean menstrual cycle length preoperatively among those categorized as ovulatory and anovulatory was 27.3 and 127.5 days, respectively. Of the 98 patients who were anovulatory preoperatively, 70 patients (71.4%) regained normal menstrual cycles after surgery. Those patients who regained ovulation had greater weight loss than those who remained anovulatory (61.4 kg vs 49.9 kg, P=0.02). Conclusions: Anovulation resulting in abnormal menses is a common problem in morbidly obese premenopausal women. The menstrual cycle disorders may completely resolve after bariatric surgery. Thus, infertility due to anovulation among morbidly obese women could potentially be viewed as an additional indication for bariatric surgery.

The impact of bariatric surgery on menstrual patterns.

Baking soda pica: a case of hypokalemic metabolic alkalosis and rhabdomyolysis in pregnancy

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Anti-TNF therapy: Is this our answer to pyoderma gangrenosum

https://www.cghjournal.org/article/S1542-3565(09)01199-9/pdf

Gastric ulceration in a patient treated with SIR-spheres.

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