The goals of this research proposal are to further our understanding of the reproductive aging process in women and to improve our ability to clinically assess and model reproductive aging. Reproductive aging is a continuous process that begins many years prior to menopause. Women in their late 30s and early 40s usually maintain normal menstrual function and ovulatory status, yet fertility in these women is considerably compromised compared to younger women. The primary mechanism of reproductive aging is through the process of ovarian primordial follicle (egg) depletion, a process that exhibits considerable variation between women. As a result, the age at which an individual begins to experience infertility and menstrual cycle changes secondary to follicle depletion also varies significantly and is difficult to predict. The clinical assessment of the number of primordial follicles remaining in the ovary has traditionally relied upon the measurement of ovarian or pituitary hormones such as FSH, estradiol, and inhibin B. Unfortunately, these measures are all indirect and poorly sensitive in the assessment of ovarian reserve. More recently, serum levels of anti-Müllerian hormone (AMH) and the ovarian antral follicle count have been utilized as clinical measures of ovarian reserve. Both have been correlated with chronological age and have some predictive power in determining stimulation quantity (the number of oocytes obtained at the time of egg-recovery) in in-vitro fertilization (IVF) treatment cycles. Reproductive aging in women; however, is more than just the depletion of oocytes from a woman's ovaries, but also involves a decline in oocyte quality. The predictive value of these clinical markers of ovarian reserve with regards to oocyte quality is unknown. Additionally, new tools developed to assess biological aging in other organ systems such as white blood cell telomere length and the measurement of advanced glycation end products (AGEs) through skin autofluorescence have not been evaluated with respect to the reproductive aging process. This proposal seeks to develop better models of normal female reproductive aging by identifying novel markers of ovarian reserve and determining their relationship with both oocyte quantity and quality obtained during IVF treatment cycles.

To test our hypotheses, we will enroll 120 healthy women undergoing ART cycles at OU Physicians Reproductive Health.

Patients undergoing an ART treatment cycle at the OU Physicians Reproductive Health clinic will be approached regarding enrollment.

• informed consent
• collection of baseline demographic data (height, weight, ethnicity, age)
• cycle-day 3 measurements of FSH, estradiol, inhibin B, AMH, white-blood cells for telomere length assay, and measurement of hemoglobin A1C to control for blood glucose levels
• AFC as determined by transvaginal ultrasound exam
• skin autofluorescence measurement
• subjects then undergo IVF as directed by their physician
• outcome measures include number of oocytes recovered, peak estradiol, quantity of gonadotropins utilized during the course of treatment, and assessment of oocyte quality by morphology assessment with light microscopy.

Inclusion Criteria:

• Undergoing an ART treatment cycle

• Age range 18-44 years old

  • NOTE: Must be willing to travel to Oklahoma City to participate. Need to have the transvaginal ultrasound and skin autofluorescence measurement at the OU Physicians Reproductive Health Clinic in Oklahoma City, Oklahoma
  • NOTE: Study will not pay for ART/IVF treatment.

Exclusion Criteria:

• Gynecological malignancy
• chemotherapy or radiation therapy treatment
• Autoimmune disease
• Prior ovarian surgery
• Ovarian pathology

Patients undergoing an ART treatment cycle at the OU Physicians Reproductive Health clinic in Oklahoma City, Oklahoma will be approached regarding enrollment.

NOTE: Must be willing to travel to Oklahoma City to participate. Need to have the transvaginal ultrasound and skin autofluorescence measurement at the OU Physicians Reproductive Health Clinic in Oklahoma City, Oklahoma