Association between body mass index, weight loss and the chance of pregnancy in women with polycystic ovary syndrome and overweight or obesity: a retrospective cohort study in the UK

Abstract

Study question: What are the associations between baseline BMI (Study 1) and change in body weight (Study 2) with the likelihood of pregnancy in women with polycystic ovary syndrome (PCOS).

Summary answer: In women with PCOS, higher baseline BMI was associated with a lower chance of pregnancy; however, weight loss was associated with an increased chance of pregnancy versus maintaining a stable weight or gaining weight.

What is known already: Two studies in large cohorts of Danish women with the intention to become pregnant showed a decline in fecundability ratios with higher BMI. Furthermore, a meta-analysis found that overweight/obesity significantly worsened metabolic and reproductive outcomes in women with PCOS.

Study design, size, duration: Data were extracted from the UK Clinical Practice Research Datalink GOLD database. Patients included women aged 18-45 years with BMI ≥18.5 (Study 1) or ≥25 kg/m2 (Study 2) at time of PCOS diagnosis (index date). The primary outcome was the time to first pregnancy recorded during 36-months' follow-up, analysed with Cox proportional hazard models and presented as hazard ratios (HRs).

Participants/materials, setting, methods: Study 1 included 9955 women with PCOS. Study 2 included 7593 women with PCOS and median BMI of 34.0 kg/m2.

Main results and the role of chance: Higher BMI was associated with a lower chance of pregnancy in the 3 years following diagnosis. It was estimated that 41% of women with normal weight (18.5-24.9 kg/m2) would become pregnant compared to 17% of women with obesity class III (BMI ≥40.0 kg/m2) during follow-up. Furthermore, the chance of pregnancy for women with obesity class III was estimated to be 63% lower than for women with normal weight, with the same age and glycaemic status (HR 0.37, 95% CI 0.31-0.44; P < 0.0001). A significant inverse association was found between BMI change and chance of pregnancy: 10% weight loss was estimated to increase the chance of pregnancy by 68% for women with baseline BMI of 40 kg/m2 (HR 1.68, 95% CI 1.49-1.90).

Limitations, reasons for caution: Multiple factors influence the chance of pregnancy (the ability and willingness to become pregnant), which was addressed by exclusion criteria employed. The real-world nature of the study means that use of non-prescription contraceptives was not available. Bias may have been introduced by the fact that only around 40% of women with PCOS in the CPRD GOLD database had their BMI recorded during the year prior to PCOS diagnosis. BMI categories used in the analyses may not be applicable to women of all ethnicities. The study population was only representative of women in the UK and results may not be generalizable to other regions. PCOS diagnoses were based on codes entered into the system by primary care providers, and no information was available regarding the criteria used for diagnosis, although symptoms used to diagnose PCOS have not changed over time.

Wider implications of the findings: Our observations provide further evidence of the benefits of weight loss in women with overweight/obesity and PCOS who are seeking to become pregnant.

Study funding/competing interest(s): Novo Nordisk A/S. A.H.B. declares fees for consultancy from Novo Nordisk. P.N.L. and C.L.H. are employees of Novo Nordisk. V.S. and A.V. are employees of, and hold shares in, Novo Nordisk.

Trial registration number: N/A.

Keywords: BMI; cohort study; fecundity; obesity; overweight; polycystic ovary syndrome; pregnancy; weight loss.

Figure 1.

Estimated cumulative incidence of pregnancies for women with polycystic ovary syndrome (PCOS) by BMI category in the with 3-year follow-up. Analysis performed using data from the Study 1 cohort (N = 9955), which was sampled to evaluate the association between BMI and chance of pregnancy. The cumulative pregnancy rate during follow-up of up to 3 years across the five BMI categories was estimated using the Kaplan–Meier method. The lines indicate the cumulative estimated mean proportion of patients with pregnancy. The shaded areas show the 95% CI.

Figure 2.

Chance of pregnancy by baseline BMI category. Analysis performed using data from the Study 1 cohort (N = 9955), which was sampled to evaluate the association between BMI category and chance of pregnancy relative to normal weight. Diamonds indicate hazard ratios for pregnancy by baseline BMI categories, calculated using a Cox proportional hazard model. The horizontal lines indicate the 95% CIs. The model was adjusted for glycaemic status (diabetes or glycated haemoglobin ≥6.0%; HR 0.74, 95% CI 0.54–1.02; P = 0.066) and age as a quadratic term (HR 0.990, 95% CI 0.988–0.991; P < 0.0001). HR, hazard ratio.

Figure 3.

Chance of pregnancy across the range of ages at polycystic ovary syndrome (PCOS) diagnosis by BMI category. Analysis performed using data from the Study 1 cohort (N = 9955), which was sampled to evaluate the association between BMI and chance of pregnancy. This plot shows the hazard ratios at different ages for the five BMI categories (18.5–24.9 kg/m² (normal weight), 25.0–29.9 kg/m² (overweight), 30.0–34.9 kg/m² (obesity class I), 35.0–39.9 kg/m² (obesity class II) and ≥40.0 kg/m² (obesity class III)), as estimated by the Cox proportional hazard model, using women with normal BMI and an age of 27 at PCOS diagnosis as the reference. The plot allows identification of women with different ages and BMI categories who are estimated to have equal chance of pregnancy, as illustrated by the highlighted data points for women aged 35 years with normal weight and women aged 31 years with obesity class II.

Figure 4.

Chance of pregnancy for selected body weight changes by baseline BMI. Analysis performed using data from the Study 2 cohort (N = 7593), which was sampled to evaluate the association between weight loss and chance of pregnancy. The plot illustrates the chance of pregnancy, as estimated by the Cox proportional hazard model, across the full baseline BMI range for selected body weight changes (5% weight gain and 5%, 10% and 15% weight loss). The reference is stable weight (no weight change) as shown by the grey line. The estimated chance of pregnancy was calculated with the 95% CIs for each individual BMI value and visualized as continuous lines across the full range.

Figure 5.

Chance of pregnancy for selected body weight changes for three example baseline BMIs. Analysis performed using data from the Study 2 cohort (N = 7593), which was sampled to evaluate the association between weight loss and chance of pregnancy. The three plots illustrate the chance of pregnancy, as estimated by the Cox proportional hazard model, with 95% CI (shaded areas) for selected example baseline BMIs of 30, 40 and 50 kg/m², relative to stable weight (no weight change), as depicted by the grey data point. These data represent a subset of the data reported in Figure 4. By assumption, the model prescribes a log-linear relationship between weight change and the chance of pregnancy, and due to this log-linear relationship, a straight line can be drawn through the point estimates at 5% weight gain and 5%, 10% and 15% weight loss.