By Makenzie Hamilton, DO
September 4, 2019

Editor’s Note: September is Polycystic Ovary Syndrome (PCOS) Awareness Month, and we join the many organizations raising awareness and providing education about this common condition. PCOS affects 10-15% of women and is the leading cause of female infertility. It is also associated with medical conditions like type 2 diabetes, cardiovascular disease, and obesity, among others.

Below is a review of thought-provoking research[i] published in the Journal of Electron Microscopy titled, “Scanning electron and light microscopy study of the cervical mucus in women with polycystic ovary syndrome.” It was written by Makenzie Hamilton, DO as part of a two-week elective taught by FACTS executive director, Dr. Marguerite Duane, at Georgetown University College of Medicine. Its findings highlight the need for further research to assess root causes behind infertility in PCOS to facilitate its prevention and more targeted and effective treatment.

Background
Cervical mucus is a critical component of female fertility. In response to female hormones, its chemical makeup, physical properties, and ultrastructure change throughout the menstrual cycle. These changes facilitate or block the passage of sperm. Without appropriate changes in the cervical mucus during the various phases of the menstrual cycle, achieving pregnancy can be difficult or impossible.

Polycystic ovary syndrome (PCOS) is a common cause of infertility in women. While there are likely multiple contributing factors to this infertility, changes in cervical mucus may play a significant role. In this small but valuable study, researchers assess the ultrastructure and crystallization patterns of cervical mucus using light microscopy and scanning electron microscopy to analyze differences between women with and without PCOS.

Methodology
After ensuring appropriate bioethics approval, the researchers selected 10 women to participate in the study. The group included 4 women with normal ovulatory cycles who served as control subjects, 2 women with PCOS and ovulatory cycles, and 4 women with PCOS and anovulatory cycles. Women with other disorders that can contribute to infertility (thyroid disorders, congenital adrenal hyperplasia, etc.) were excluded from the study.

Using measurements of urinary hormone metabolites (estrone glucuronide, a metabolite of estrogen, and pregnanediol glucuronide, a metabolite of progesterone), the researchers determined the phase of the menstrual cycle for each woman and whether they were ovulatory or anovulatory. As a cross-check, transvaginal ultrasound was performed to observe the development of the ovarian follicle and the width of the endometrium to confirm the phase.

Cervical mucus samples were then obtained via aspiration during the periovulatory period. These samples were observed using a scanning electron microscope to assess ultrastructure and under light microscopy to identify the crystallization pattern.

Results
The study found that while women with PCOS and ovulatory cycles had periovulatory hormone levels similar to women in the control group, those with anovulatory cycles had significantly lower estrogen and higher progesterone hormone metabolite levels. The changes in ultrastructure of the cervical mucus as seen under a scanning electron microscope were especially intriguing. The mucus of women in the control group and women with PCOS and ovulatory cycles showed normal laxity and pore size, with an average pore diameter of 8.4 micrometers. However, the ultrastructure in the mucus of women with PCOS and anovulatory cycles was shown to be significantly denser, with an average pore diameter of 1.8 micrometers.

In assessing crystallization by light microscopy, significant differences were also observed. The cervical mucus of women in the control group showed a “well-defined, identifiable pattern and a symmetric arrangement” with type L and type S mucus, with L-type being a normal mucus seen throughout the menstrual cycle and S-type mucus being the most fertile-type mucus. The cervical mucus of women with PCOS and ovulatory cycles showed crystallization similar to L-type mucus. The cervical mucus of women with PCOS and anovulatory cycles showed “poorly defined and atypical crystallization,” resembling type G mucus, the least fertile mucus.

Discussion
The researchers conducting this study noted important findings about the relationship between PCOS and changes in cervical mucus. Ultimately, women with PCOS and ovulatory cycles had cervical mucus with similar properties as women with normal ovulatory cycles. However, women with PCOS and anovulatory cycles were found to have cervical mucus that is more compact and less symmetric. The changes seen in the cervical mucus in these women likely contribute to having a more dense, impenetrable mucus, making passage of sperm difficult and thereby contributing to their infertility. The crystallization findings in women with PCOS were also significantly different from the patterns seen in women with normal cycles.

This study is the first to establish the important relationship between PCOS and changes in cervical mucus ultrastructure and crystallization, and the first to state these changes likely contribute to infertility. Correlating their results with changes in hormone levels during the periovulatory period makes their research especially useful. It will be essential for future studies to include larger sample sizes of women and delve deeper into the make-up of cervical mucus, including details on glycoproteins like mucin. More research on this topic may lead to more effective therapeutic modalities for women with PCOS who struggle with infertility.

Editor’s Note: FACTS exists to facilitate such learning and ensure the information medical professionals receive about fertility awareness based methods (FABMs) is accurate and up-to-date. For a patient story about the use of FABMs in the diagnosis and treatment of PCOS, read Beyond Family Planning: Using FABMs for PCOS.

REFERENCES
[i] Vigil L, Cortes M, Zuniga A, Riquelme J, Ceric F. Scanning electron and light microscopy study of the cervical mucus in women with polycystic ovary syndrome. Journal of Electron Microscopy. 2009;58(1): 21-27.

 

Author Bio: Makenzie Hamilton, DO completed medical school at Kansas City University of Medicine and Biosciences. She is a first year resident pursuing a career in pediatrics. By applying all she learned during the FACTS elective, she plans to educate adolescent patients and their mothers on the option and benefits of FABMs. “I believe these methods are underutilized and incredibly beneficial for many patients,” she explains. “I also hope to introduce medical students to the benefits of FABMs, as these are not covered adequately within most medical school curricula.” She plans to continue to study this important subject on her own.

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