Ovarian Ultrasonography for the Clinical Evaluation of Polycystic Ovary Syndrome
Ovarian Ultrasonography for the Clinical Evaluation of Polycystic Ovary Syndrome
The investigators would like to determine how aspects of adiposity and age influence
 ultrasound features of the ovaries which are used to diagnose polycystic ovarian syndrome
 (PCOS). The study will also compare anti-Müllerian hormone (AMH) levels against ultrasound
 features of the ovary to predict PCOS.
The purpose of this study is to develop ultrasound criteria for polycystic ovaries for women
 with PCOS across early, mid and late adulthood and to assess the impact of body composition
 on these ultrasound criteria.. The study will also compare ultrasound features of the ovary
 against or in combination with AMH (a hormonal biomarker) in predicting PCOS. This research
 will help improve the diagnosis of PCOS by considering multiple markers (i.e., ultrasound
 features and AMH levels) and multiple modifiers of those markers (i.e., age and adiposity).

 As the name implies, the primary ultrasound feature used to diagnose PCOS is polycystic
 ovaries (PCO). However, PCO have frequently been observed in healthy women, calling into
 question the specificity of PCO to the condition of PCOS, as well as its ability to inform
 progression of the disease and/or response to treatment. The Lujan laboratory recently showed
 that the most widely accepted ultrasound criteria for PCO overlap with features of the normal
 ovary, and their laboratory proposed new thresholds to redefine PCO. These new criteria
 represented a significant change in the definition of PCO owing to the improved resolution of
 new technology. That said, these new criteria are still limited. They do not account for
 factors known or suspected to influence ovarian morphology. For example, follicle counts and
 ovarian size increase at puberty and decrease with age. Additional results from the Lujan
 laboratory showed that follicle number per ovary (FNPO) thresholds for women in later
 adulthood (35-38y) were substantially lower than those in early (18-25y) and mid-adulthood
 (26-34y). Furthermore, the new criteria for PCO do not account for a potential impact of
 adiposity on ovarian morphology. In the same study, conducted by the Lujan laboratory,
 overweight women exhibited more 6-9mm follicles than lean women, irrespective of androgen
 status.

 Lastly, there is significant interest in determining whether AMH can serve as a surrogate to
 sonographic measures to define PCO. AMH is a peptide hormone produced by the granulosa cells
 of growing follicles and circulating levels represent secretions by antral follicles ≤8mm.
 Accordingly, serum AMH is increased in women with PCOS, reflecting the accumulation of 2-5mm
 antral follicles and greater production by granulosa cells of PCO compared to normal ovaries.
 Excess AMH is thought to inhibit follicle growth and selection. Unlike discrete aspects of
 ovarian morphology (i.e. follicle number or size),85 AMH levels remain largely constant
 throughout the normal menstrual cycle.Such stability may make AMH a more advantageous
 functional and surrogate morphological indicator of ovarian status compared to morphologic
 features. Further, some have argued that the variability in ultrasound assessments, and
 unsuitability of transvaginal approaches in certain clinical populations, justify the pursuit
 of a less onerous biomarker of PCO. However, there is significant bias across AMH assays and
 a consensual threshold for AMH to define PCO has not been determined. Proposed thresholds
 were hindered by heterogeneity in assay performance and in the clinical cohorts assessed.
 Ultimately, the ability of AMH to serve as a surrogate marker for PCO remains unknown and
 should be evaluated against sonographic measures in well-defined cohorts with improved
 assays. In this study, the researchers plan to refine the sonographic definition of PCO by
 establishing age-specific criteria that maintain sensitivity and specificity for PCOS in both
 lean and overweight populations. They will also clarify any ability of anti-Müllerian hormone
 (AMH) to better inform the diagnosis of PCOS.

 To accomplish these objectives, the investigators plan to recruit 120 women with regular
 ovulatory cycles and 120 women with PCOS. Within each of these categories, the investigators
 plan to recruit 20 lean and 20 overweight women in each age group: 18-24y (early), 25-34y
 (mid), ≥35y (later adulthood). Ultrasound scans of the ovaries will be assessed for the total
 number, size, and distribution of follicles using both two- and three-dimensional imaging
 techniques. Additionally, participants will have blood samples collected to determine serum
 concentrations of AMH. Because features of the ovaries are expected to be different in lean
 and overweight women, the researchers hope to develop ultrasound criteria that will help
 healthcare providers to diagnosis specific ovulation problems in women across all body sizes
 and ages. This project addresses the need to improve methods and criteria used to define PCO
 across clinical populations.
Inclusion Criteria:

 -  Aged >18 years

 -  At least 2y post-menarche

 -  BMI >18.5kg/m2

 -  Good visibility of the ovaries on ultrasound

 -  Pelvic exam with normal results within the last 2 years

 Either:

 -  Regular menstrual cycles (21-35 days);

 -  Irregular menstrual cycles (>36 days); or

 -  Previous diagnosis of PCOS from a primary care provider

 Exclusion Criteria:

 -  Use of medication(s) known or suspected to interfere with reproductive function,
 metabolism, and/or appetite (e.g., oral contraceptives) within the past 3 months

 -  Use of fertility medications in the past 2 months (e.g., Clomid)

 -  Current use of a non-copper intrauterine device for contraception (e.g., Mirena)

 -  Diagnosis of premature ovarian failure, endometriosis, or another disease/disorder
 (other than PCOS) known or suspected to interfere with reproductive function

 -  History of ovarian surgery

 -  Missing uterus or an ovary

 -  Pregnant or breastfeeding

 -  Diagnosis of a bleeding disorder

 -  Regular use of blood thinners/anticoagulants

 -  Skin allergy/condition that might be aggravated by alcohol application

 -  Currently being treated for a vaginal infection, cervical infection, sexually
 transmitted infection, or disease either with antibiotics, antifungals, or anti-viral
 medication

 -  Abnormal vaginal discharge, pelvic pain, and/or blisters/lesions/warts/skin growths in
 the genital/anal area, which have not been examined by a medical professional.

 -  Vaginal abnormality (e.g., vaginal atresia/hypoplasia, vaginal septation, Mullerian
 agenesis, vulvar/vaginal malignancy).

 -  Not otherwise healthy