1. Basic Female Infertility for the Primary Care Physician
Molly Moravek, MD, MPH
Director, Fertility Preservation Program
Assistant Professor
Reproductive Endocrinology and Infertility
Department of Obstetrics and Gynecology

2. Objectives Recognize common causes of female infertility
Understand the basic female infertility workup be able to interpret the results
Briefly describe treatment options

3. Definitions Fertility The ability to conceive and produce offspring
Infertility
The inability to conceive after 12 months of frequent intercourse without contraception
Fecundability
The probability that a single cycle will result in pregnancy
Fecundity
The probability that a single cycle will result in a live birth

4. Epidemiology (CDC )
Women aged with impaired fecundity: 7.5 million (12.3%)
Married women aged that are infertile: 1.0 million (6.1%)
Women aged who have ever used infertility services: 6.9 million (11.3%)

5. Normal Reproduction
Education on normal human reproductive efficiency can help provide important perspective for an infertile couple
In normally fertile couples, cycle fecundability is ~20% and does not exceed 35%, even with carefully timed intercourse
3 months of “trying”  57% will become pregnant
6 mo  72%
1 yr  85%
2 yrs  93%

6. Tubal and Pelvic Pathology Ovulatory Dysfunction
Female Infertility
Tubal and Pelvic Pathology
40%
Ovulatory Dysfunction
40%
Male Causes
35%
Female Causes
50%
Unexplained Causes
15%
Unusual Problems
10%
Unexplained
Infertility
10%

7. Evaluation – Female Infertility
History
General Physical Exam
Endocrine blood tests
Evaluation of uterine cavity/tubal patency

8. Key Components + + =

9. Tests of Ovarian Reserve
Day 3 FSH/E2
FSH > 10 to 15 IU/L on day 2 or 3 is considered DOR
Anti-mullerian hormone (AMH)
Antral follicle count (AFC)

12. Age and Reproduction
Data from natural populations suggest that fertility in women peaks between 20-24yo, decreases gradually until 30-32yo, then declines more rapidly
Overall, fertility rates are:
4-8% lower in women aged 25-29yo
15-19% lower in women aged 30-34yo
26-46% lower in women aged 35-39yo
Up to 95% lower in women aged 40-45yo
As women age, miscarriage rates also increase
e.g. Hutterites

14. Other Endocrine Testing
TSH – goal <2.5 mU/L
Prolactin?
Androgens?
Midluteal progesterone?

15. Hyperprolactinemia Eating Medications Hypothyroidism
Pituitary Disorders
Chest wall stimulation
Hyperprolactinemia
Stress
Breastfeeding
Infiltrative Diseases
Adrenal Insufficiency
Idiopathic
Intercourse

16. Anatomical Evaluation
Hysterosalpingogram (HSG)
Saline infusion sonogram (SIS)
Pelvic ultrasound

17. Hysterosalpingogram #1

18. Hysterosalpingogram #2

19. Saline Infusion Sonography

20. Semen Analysis Parameter WHO 1999 WHO 2010 Volume 2 ml 1.5 ml
Concentration
20 million/ml
  15 million/ml
Progressive motility
50%
32%
Normal forms
14%   4%

21. Hypothalamic Amenorrhea
Most common cause of hypogonadotropic amenorrhea
Categorized by:
Low/normal gonadotropins
Low E2
Normal prolactin/TSH levels
Normal imaging evaluation of the sella turcica
Failure to demonstrate withdrawal bleeding
Associated with eating disorders, excessive exercise, extreme stress
Every women’s set point Is somewhere different for amount of weight loss or amount of stress/exercise that will shut down HPO axis. May be less than you think. It is thought that minimum body fat necessary to initiate menarche is 17%.

22. PCOS Most common endocrine disorder Rotterdam Criteria (2 of 3):
Oligo-/Anovulation
Hyperandrogenism
Polycystic ovaries
Increased risk of endometrial hyperplasia or carcinoma
Increased insulin resistance, NIDDM – 2hr GTT
Metabolic syndrome/Central obesity - Lipids

23. It is imperative to rule out other causes of hyperandrogenism before diagnosing PCOS

24. Evaluation of Androgen Excess
Testosterone (LCMS)
Elevation consistent with PCO
Very high levels >200 ng/dL suggest tumor
DHEAS
Elevated levels indicate adrenal source (>700ug/dL)
17-hydroxyprogesterone
Assess in follicular phase, AM
Elevated level could indicate CAH

25. PCOS Treatment Cycle Regulation/Endometrial protection Hyperandogenism
OCPs
Cyclic progesterone
Hyperandogenism
Spironolactone
Insulin Resistance/Hyperlipidemia
Infertility
Letrozole likely superior to clomiphene

26. Unexplained infertility
Diagnosis of exclusion
Incidence 10-30% among infertile populations
2 potential explanations
There truly is NO abnormality and the couple’s natural fertility is at the extreme lower end of normal range
There is a specific cause, but not one that we can identify with the existing tests

27. Recurrent Pregnancy Loss
Pregnancy occurs in ~15% of clinical pregnancies
Age dependent
Majority SAB <10 weeks’ gestation due to random chromosome errors
>90% of conceptions with nl karyotype will continue
<5% of women have 2 consecutive miscarriages
Only ~1% experience 3 or more
Diagnosis made and treated in about 50% of women with RPL

28. Recurrent Pregnancy Loss
Recurrent pregnancy loss defined as 3+ (do not have to be consecutive)
Evaluation warranted after 2 losses (preferably documented), especially when:
Fetal heart activity noted prior to loss
Nl karyotype on POC
Age >35
Infertility

30. Etiology Undisputed: Not so firmly established:
Genetic: Balanced translocation in either partner, maternal age, oocyte quality, random mutations
Anatomic: Congenital and acquired uterine anomalies (usually later losses)
Immunologic: Thrombotic complications of antiphospholipid syndrome
Not so firmly established:
Alloimmunopathology
Inherited thrombophilias, e.g. FVL
Endocrinopathies: Thyroid, DM, luteal phase defects
Infections: Genital mycoplasma
Environmental: tobacco, alcohol, caffeine

31. Management options

32. Lifestyle Changes Weight loss if BMI > 30 Smoking cessation
Drug use cessation
Decrease in caffeine
Decrease in life stressors

33. Ovulation Induction/Superovulation
Clomiphene citrate
Letrozole
Gonadotropins
+/- IUI

34. In Vitro Fertilization (IVF)

35. Preimplantation Genetic Diagnosis

36. Third Party Reproduction
Donor Oocytes
Donor Embryos
Gestational Carrier

38. Shameless Plug for the Fertility Preservation Program 

39. Cancer and Fertility Survival rates are at an all-time high
Treatment is often detrimental to reproductive function
Resumption of menses ≠ fertility
An infertility diagnosis has equivalent psychosocial effects as a cancer diagnosis
Treatment of these cancers is often detrimental to reproductive function

40. Options Females Males Embryo Cryopreservation Oocyte Cryopreservation
Ovarian Shielding
Ovarian Transposition
GnRH Agonist
Ovarian Tissue Cryopreservation
Sperm banking
Testicular sperm extraction
Testicular shielding
Testicular tissue cryopreservation

41. If you’re just waking up….
Evaluate women >1 year without conception (>6 months if >35yo), 2+ miscarriages, oligo-/amennorhea
Basic infertility workup prior to referral:
Day 3 FSH and E2
AMH, TSH
Other labs as indicated by history
Semen analysis

42. Thank You!