Polycystic ovarian syndrome among women diagnosed with infertility in the Gulf Cooperation Council countries: A protocol for systematic review and meta-analysis of prevalence studies

Abstract

Background:

Polycystic ovarian syndrome, a common endocrine disorder, is an important cause of infertility among women of reproductive age. Within the Gulf Cooperation Council countries, polycystic ovarian syndrome is found to affect women increasingly. No study has been carried out to critically summarize the evidence on the prevalence of polycystic ovarian syndrome among women suffering from infertility in these countries.

Objective:

This protocol aims to conduct a systematic review and meta-analysis of the studies reporting the prevalence of polycystic ovarian syndrome among women seeking infertility treatment in the six Gulf Cooperation Council countries (Bahrain, Kuwait, Oman, Saudi Arabia, Qatar, and United Arab Emirates).

Design/Methods and analysis:

The systematic review and meta-analysis will follow the following method.

Data source:

Five databases, including PubMed, Embase, CINAHL, Web of Science, and SCOPUS, will be searched for observational studies using a combination of relevant keywords and Medical Subject Headings from inception of databases.

Data extraction:

Two reviewers will screen titles and abstracts, followed by a full-text search based on the eligibility criteria. The main outcome is to measure the proportion of women who have polycystic ovarian syndrome among infertility-diagnosed patients. In addition, the risk of bias in the included studies will be assessed using the national institute of health quality assessment tool for observational studies.

Data synthesis:

The random-effects method of the analysis with the inverse variance will be used to calculate the pooled prevalence of polycystic ovarian syndrome–attributed infertility. Variation in prevalence estimates will be calculated using subgroup analysis based on study and patients’ characteristics and publication bias will be assessed via funnel plot inspection and Eggar’s test.

Discussion:

A critical assessment of evidence on the prevalence of polycystic ovarian syndrome in women attending fertility clinics is helpful in risk quantification, enabling better planning for managing infertility in women with polycystic ovarian syndrome.

Registration:

This protocol has been registered with PROSPERO, protocol registration number (CRD42022355087).

Introduction

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder among women of reproductive age characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. ¹ Globally, the prevalence of PCOS among the women of reproductive age was reported to range from 6% to 10%. ² Named as Stein Leventhal syndrome previously, ³ PCOS results from an imbalance of sex hormones, leading to the formation of multiple ovarian follicles or cysts, menstrual abnormalities, and clinical and/or biochemical hyperandrogenism. Major risk factors that predispose females towards development of PCOS include obesity, physical inactivity, family history, and environmental toxicity.^4,5 The main clinical features of PCOS include weight gain, insulin resistance, male-pattern baldness, hirsutism and acne. ⁴

Furthermore, PCOS has been found to impose psychological stress resulting in mood swings, low self-esteem, depression and anxiety. ⁶ Therefore, PCOS significantly impacts women’s psychological health and quality of life. Moreover, PCOS may lead to grave complications such as diabetes, cardiovascular disease and endometrial cancer, which can potentially be prevented by early diagnosis. ²

Infertility is defined as the inability to achieve a clinical pregnancy after 1 year of regular, unprotected sexual intercourse. ⁷ It is evident from the literature that subfertility and the risk of pregnancy-related complications are significantly increased among women with PCOS. ⁸ Infertility affects 8%–12% of people of reproductive age worldwide. ⁷ Whereas 80% of women who complain of anovulatory infertility have been reported to have PCOS. ⁹

The PCOS treatment strategy consists of lifestyle modifications, followed by medical treatment, including hormonal contraceptives, letrozole and clomiphene citrate.^10,11 Therefore, estimation of the burden of PCOS among infertile women can help provide better-targeted healthcare, thus achieving fertility.

A recent review summarized the prevalence of PCOS in women from different ethnicities, including Asian, Hispanic, African American, Greek Islander, and Indigenous Australian. However, the review did not include any information on women from Arabic background. ¹² Another review summarized the global PCOS prevalence among adolescent women to range from 6% and 10% based on different diagnostic criteria. ¹³ In the US female population, PCOS prevalence ranged from 10.3% to 47.5%. ¹⁴ Several individual studies have been conducted to estimate the prevalence of PCOS among general women population of individual Gulf Cooperation Council (GCC) countries such as in Oman, Qatar, Saudi Arabia and United Arab Emirates.^15–18 Similarly, although there is a limited evidence on the prevalence of infertility in the individual GCC countries, a review of studies on infertility in the Middle East and North Africa (MENA) region reported clinical fertility to be 17.2% and demographic fertility to be 38.5%. ¹⁹ But no study has yet summarized the overall prevalence of PCOS among infertile women in these countries. To address this gap in evidence, this protocol aims to provide evidence on the prevalence of PCOS among infertile women in the six GCC countries (Bahrain, Kuwait, Oman, Saudi Arabia, Qatar and United Arab Emirates).

Methods

Protocol and registration

This protocol has been prepared in accordance with the guidelines of PRISMA-P ²⁰ (Checklist included in Supplemental file 1). The protocol has been registered with The International Prospective Register of Systematic Reviews (PROSPERO); protocol registration number (CRD42022355087). The systematic review and meta-analysis will be reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement-2020. ²¹

Eligibility criteria

The criteria to assess the eligibility of studies for inclusion in this systematic review and meta-analysis is designed following the PECO (Population, Exposure, Comparison and Outcome) approach. ²²

Population

Our population of interest will be all women diagnosed with infertility or women seeking fertility treatment or consultation in the six GCC countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and UAE). Women will be included irrespective of their age, duration of the marriage, parity, type of infertility, cause of infertility and the sample size.

Exposure

Infertility will be our exposure of interest. Studies addressing gynaecological abnormalities and diseases other than infertility will not be considered.

Outcome

PCOS is our outcome of interest. Studies reporting on the prevalence or those allowing to calculate the prevalence of PCOS in our population of interest will be included. The diagnosis of PCOS will not be based on any specific diagnostic criteria to ensure maximum coverage of studies.

Study design

All quantitative observational epidemiological studies, including cross-sectional and cohort studies, will be included. Case–control studies will be included as long as the cases are infertile women and not the women diagnosed with PCOS, as this will not allow estimation of PCOS prevalence. Interventional and qualitative studies and those without a clear study design will be excluded.

Setting

No exclusion based on setting will be applied; studies conducted anywhere, clinical or non-clinical, will be included. Self-reported population-based studies will be excluded.

Publications

Peer-reviewed studies in English or Arabic language will be included. Publications to be also considered eligible, should be observational in design and reporting a calculated or calculable prevalence of the PCOS in the study population of interest. Case and case series studies, editorials, letters to editors, conference proceedings without complete data on outcome measures, studies lacking full-text and local reports will also be excluded. Pre-prints and publications in grey literatures will be also excluded. Bibliographies of mini-reviews, scoping and systematic reviews will be searched for any potentially eligible studies.

Data sources and search strategy

Five core medical and health science databases PubMed, Web of Science, Cumulative Index to Nursing and Allied Health literature (CINAHL), Embase and SCOPUS will be searched on September 2022. A combination of systematically selected search terms will be applied using the search fields: title, abstract, keywords (alternatively ‘topic’) and the MeSH (Medical Subject Headings) or Thesaurus. The terms representing all GCC countries, along with PCOS and their possible variants, will be applied so that no study is missed out. No language filter or time limitation will be applied. The search will be updated ahead of the manuscript submission. Preliminary search strategy for PubMed and Scopus conducted in June, 2022 is reported in the Supplemental file 2. The bibliography of included studies will be searched for other potential publications. Assistance from the medical librarian will be taken to enhance the results from the databases. The retrieved results will be managed using the blinded screening software Covidence. ²³

Study screening

The retrieved studies will be screened via a two-step process by at least two reviewers. After the automatic removal of duplicates, a manual check will be performed for any remaining duplicates. For screening, first, the titles and abstracts of studies will be screened to include those reporting on the prevalence of PCOS in the six GCC countries. In the next step, the full text of studies chosen during the first step will be screened to ensure the suitability of included studies against eligibility criteria. In addition, bibliographies of the included studies will also be screened for any eligible studies that could have been missed during the screening process. Any discrepancies between the reviewers will be resolved by an independent reviewer, different than the screeners, by using the blinded conflict resolution function in Covidence.

Data extraction

Data will be extracted on predefined fields in Covidence, by at least two reviewers independently. Fields for which data will be populated include publication details (author and year), study details (geographic location, setting, design, and period), participant details (age, sample size, number of infertile women), the method for recruitment and the outcome measure assessment, diagnostic criteria and results and outcome measure (prevalence: number of women diagnosed with PCOS). The data extraction fields will first be piloted for five studies. The authors will be contacted in case of missing data. Any disagreement on the extracted data will be resolved by mutual discussion among the reviewers.

Risk of bias assessment

The risk of bias (RoB) of the included studies will be assessed using the National Institute of Health (NIH) quality assessment checklist for the assessment of RoB of observational cohort and cross-sectional studies. ²⁴ The tool consists of 14 criteria, of which fields relevant to the design of studies included in the review will be used. These include clarity of research question or objective, specification of the study population, the participation rate of the eligible population, uniform application of inclusion and exclusion criteria for participant recruitment, explanation of sample size calculation, exposure and outcome measurement, the timeframe between exposure and outcome, specification of exposure measure in terms of validity, reliability and consistent implementation, assessment of exposure more than once over time, blinding of outcome assessors, loss to follow-up and consideration of key confounding variables and adjustment accordingly. This will be done by at least two reviewers independently, with the resolution of any disagreement by the involvement of the third reviewer.

Synthesis of evidence

The findings on study characteristics will be first reported narratively. The summary estimate for the prevalence will be provided based on stratification such as infertility, participant age, and year of study. If the study provides more than one stratified estimate, only one will be included to prevent double counting.

Random-effects meta-analysis will be conducted to calculate the pooled prevalence of PCOS in infertile women using the sample size and proportion of women diagnosed with PCOS. Metaprop command from STATA will be used to generate pooled proportions and pooled prevalence using inverse variance weights. ²⁵ Visual assessment of summary estimates will be obtained by forest plots, including 95% confidence intervals. Heterogeneity will be assessed by calculating the Q-statistic and Tau-squared values. These values are more reflective of between-study heterogeneity rather than I-squared (I ² ) values. In addition, a 95% prediction interval that is representing the true effect size of the included studies will be calculated. A p value of 0.1 will be considered statistically significant for all the tests.

Publication bias of the included studies will be assessed by observation of funnel plots and conduction of Egger’s test. If publication bias is found, it will be adjusted using Duval and Tweedie’s trim and fill method, ²⁶ if the number of studies allows.

Sub-group analysis

The possible variance in the prevalence of PCOS among infertile women will be observed using subgroup analysis. ²⁷ The subgroup meta-analysis to estimate the PCOS prevalence to be carried out will stratify infertile women into subgroups based on infertility type (primary and secondary) and causes. Also, a sensitivity meta-analysis will be carried out to estimate the PCOS prevalence according to the diagnostic criteria for PCOS. If sufficient data are present, additional subgroup analysis will also be performed based on, for example, geographical location, setting, quality and publication period of the studies.

Discussion

PCOS is an established cause of infertility, however, no previous reviews have assessed its burden among infertile women in the GCC countries. This systematic review and meta-analysis will consider all articles reporting on the prevalence of PCOS among the infertile women population in the region. Thus, it will provide an overall picture of PCOS-attributed infertility among women in GCC countries by providing an accurate estimate of the problem. This would contribute towards risk quantification, enabling better planning for infertility management in women with PCOS. In addition, this protocol will allow the adoption of a standardized process of conducting a systematic review and meta-analysis, via documentation and planning, as more literature continues to be published in the field of gynaecology and obstetrics. This would be of benefit to future researchers planning to undertake a systematic review and meta-analysis on a similar or related topic.

Conclusion

The proposed systematic review and meta-analysis aims to summarize the prevalence of PCOS in infertile women population in the six GCC countries. To our knowledge, this is the first systematic review and meta-analysis to assess the burden of PCOS among infertile women in these countries that share similar sociodemographic and economic characteristics. In addition, it will help determine the financial burden of infertility attributed to PCOS, thus helping early diagnosis and treatment of the condition and promoting better outcomes regarding fertility.

Supplemental Material

sj-docx-1-whe-10.1177_17455057231160940 – Supplemental material for Polycystic ovarian syndrome among women diagnosed with infertility in the Gulf Cooperation Council countries: A protocol for systematic review and meta-analysis of prevalence studies

Supplemental material, sj-docx-1-whe-10.1177_17455057231160940 for Polycystic ovarian syndrome among women diagnosed with infertility in the Gulf Cooperation Council countries: A protocol for systematic review and meta-analysis of prevalence studies by Zufishan Alam, Mohammed Altigani Abdalla, Saleh Alseiari, Mahra Alameemi, Mayytha Alzaabi, Reem Alkhoori, Linda Östlundh and Rami H. Al-Rifai in Women’s Health