Polycystic ovary syndrome (PCOS) is a common hormonal disturbance that affects women’s ovarian function. Diagnostic criteria include hyperandrogenism, irregular periods due to lack of ovulation (the release of an egg), and many small cysts in the ovaries. PCOS is affecting approximately 10% of women of reproductive age, and is the most common cause of infertility due to the lack or absence of ovulation. Many women with PCOS are also living with overweight or obesity. Weight loss is recommended in clinical PCOS guidelines as this has shown to improve the metabolic profile and general health. In addition, studies show that women living with overweight or obesity take a longer time to conceive when compared with women of normal weight. However, only few small studies have investigated how weight loss influences fertility in women diagnosed with PCOS. In this study we will include adult women of reproductive age, diagnosed with PCOS and with available body weight measurements from a database comprising data from electronic medical records for General Practitioners across the UK. As a first step we will investigate if body mass index (BMI) is associated with time to pregnancy. As a second step we will investigate if weight loss increases the chance of becoming pregnant. Given that the chance of pregnancy is increased by losing weight, we will evaluate if this chance is even greater with the greater the weight loss.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting approximately 10% of reproductive aged women. Many women with PCOS are living with overweight or obesity which also affect their ability to conceive. The evidence supporting increased reproductive function after weight loss in these women is sparse. The aim of this study is to investigate the association between weight loss and time to pregnancy. Secondary outcomes are number of pregnancies and number of Assisted Reproductive Technology (ART) treatments. Using a prospective cohort design, eligible women are aged 18 to 45 years with a diagnosis of PCOS from the Clinical Practice Research Datalink (CPRD) based on either a primary care diagnosis using the Read code classification or an ICD-10 coding from secondary care Hospital Episodes Statistics Outpatient (HES OP). Pregnancy is determined based on the first date of an event in the Pregnancy Register. Number of ART treatments are based on either a primary care diagnosis using the Read code classification or an ICD-10 coding from HES OP. Time to pregnancy will be presented and compared using Cox proportional hazards models adjusting for age, smoking status, socioeconomic status, and ethnicity. The analyses will be done in two steps. First we investigate the association between baseline BMI class (Normal weight: 18.5-24.9 kg/m2, Overweight: 25-29.9 kg/m2, Obesity class I: 30-34.9 kg/m2, Obesity class II: 35-39.9 kg/m2, Obesity class III: ≥40 kg/m2) and baseline BMI as continuous variable, respectively, and time to pregnancy. If we find an association between increased baseline BMI and time to pregnancy we will proceed with step two which is the association between percentage weight loss and time to pregnancy. To utilise all the BMI measurements available during follow-up, BMI will be included in the Cox model as a time-varying covariate. The secondary outcomes will be descriptively presented.
The primary outcome is:
• Time to pregnancy, using the first report of pregnancy captured in the CPRD Pregnancy Register, regardless of the pregnancy outcome.
The secondary outcomes are:
• Number of women who became pregnant (counts) from index date (date of PCOS diagnosis) to end of follow-up
• Number of women who received Assisted Reproductive Technology (ART*) treatment (counts) from index date to end of follow-up
*ART includes in vitro fertilization, intracytoplasmatic sperm injection and intrauterine insemination (IVF/ICSI/IUI/) and donor insemination and egg donation (1)
Esther Zimmermann - Chief Investigator - Novo Nordisk A/S
Esther Zimmermann - Corresponding Applicant - Novo Nordisk A/S
Adam Balen - Collaborator - Leeds Teaching Hospitals NHS Trust
Anette Varbo - Collaborator - Novo Nordisk A/S
Christiane L Haase - Collaborator - Novo Nordisk A/S
Tugce Kalayci Oral - Collaborator - Novo Nordisk A/S
Volker Schnecke - Collaborator - Novo Nordisk A/S
HES Outpatient;Practice Level Index of Multiple Deprivation;Pregnancy Register