Infertility PDF

INFERTILITY Authors: Eric Han MD, Elizabeth Ackley MD, and Alexander Kotlyar, MD Introductory Case A 37-year-old G0 presents with a chief complaint of inability to become pregnant. She has been actively trying to conceive for the past 2 years. She reports a long history of infrequent menses, and he...

INFERTILITY Authors: Eric Han MD, Elizabeth Ackley MD, and Alexander Kotlyar, MD Introductory Case A 37-year-old G0 presents with a chief complaint of inability to become pregnant. She has been actively trying to conceive for the past 2 years. She reports a long history of infrequent menses, and her exam is significant for obesity, with a body mass index (BMI) of 43 kg/m2 and facial acne. Her medical history is otherwise notable for hypothyroidism on Synthroid and a remote history of chlamydia as a teenager. Her partner is a 34-year-old male with no children of his own. He is generally healthy but smokes 2 packs cigarettes per day and reports occasional marijuana use. They are having unprotected intercourse approximately once a week. She is not using ovulation predictor kits. Milestone-Based Focused Questions LEVEL 1: DEMONSTRATE BASIC KNOWLEDGE ABOUT COMMON AMBULATORY GYNECOLOGIC PROBLEMS WHAT IS THE OVERALL EXPECTED LIKELIHOOD OF CONCEIVING WITHIN THE FIRST YEAR? 85% of couples conceive within the first year of regular unprotected intercourse The probability of pregnancy is highest in the first several months of unprotected intercourse (25% chance each month in the first three months), with a declining likelihood of success each subsequent month (15% per month thereafter) HOW IS INFERTILITY DEFINED? Among women < 35 years old, infertility is the inability to conceive after 12 months of regular unprotected intercourse (i.e. without the use of contraception) Among women ≥ 35 years old, this interval decreases to 6 months of regular unprotected intercourse. WHAT ARE THE CAUSES OF INFERTILITY? CAUSES OF INFERTILITY 35 30% 30% 30 25% 25 20 15 10% 10 5% 5 0 Male Factor Female Unexplained Combined Other Factor  Causes of female infertility: o Ovulatory disorders 25% o Endometriosis 15% o Pelvic adhesions 12% o Tubal blockage 11% o Other tubal abnormalities 11% o Hyperprolactinemia 7% LEVEL 2: PERFORMS THE INITIAL ASSESSMENT, FORMULATES A DIFFERENTIAL DIAGNOSIS, AND INITIATES TREATMENT FOR COMMON AMBULATORY GYNECOLOGIC PROBLEMS BASED ON HER MENSTRUAL PATTERN, YOU SUSPECT THAT THIS PATIENT HAS POLYCYSTIC OVARIAN SYNDROME (PCOS). HOW IS PCOS DIAGNOSED? Rotterdam criteria (requires at least two of the following): 1. Oligo/anovulation (fewer than 6-9 menstrual cycles per year) 2. Hyperandrogenism: clinical signs (hirsutism, acne, male pattern balding) or biochemical evidence 3. Polycystic ovaries on ultrasound: >12 follicles or increased ovarian volume (>10cm3) WHEN SHOULD AN INFERTILITY WORKUP BE INITIATED? Infertility evaluation should begin after 12 months of unprotected intercourse in women < 35 or 6 months of unprotected intercourse in women ≥ 35 years old Many experts also recommend initiating an infertility evaluation after 6 months among patients with risk factors for premature ovarian failure, advanced stage endometriosis, or suspected tubal disease HOW DO YOU INITIATE THE INFERTILITY WORKUP FOR THIS PATIENT AND HER PARTNER? The main elements that need to be evaluated are Female Factor o Ovulatory status and ovarian function o Tubal patency Male Factor o Semen Analysis Female patient Key components of history o Infertility: Duration, previous infertility workup and treatment o Complete Gyn history: menstrual pattern (cycle frequency, length, and characteristics), contraception use (current and past), history of abnormal pap smears including any past cervical procedures o Molimina symptoms prior to menses: breast tenderness, bloating, fatigue  o Sexual history: frequency of intercourse, sexual dysfunction, use of lubricants, home ovulation predictor kit use, basal body temperature measurements, sexually transmitted infections, pelvic inflammatory disease o Complete OB history: include management (medical vs surgical) of any pregnancy terminations or miscarriages, how were they performed (medically vs surgically) o Symptoms of thyroid dysfunction, galactorrhea, visual symptoms, hirsutism, pelvic and/or abdominal pain o Previous intra-abdominal infections and/or surgeries (for example, PID, ruptured appendicitis, diverticulitis, inflammatory bowel diseases) o History of chemotherapy or pelvic irradiation o Social history: Tobacco, illicit drug, alcohol use. Occupation and potential occupational or environmental exposures. Exercise, stress, changes in diet or weight. o Current medications and allergies o Family history of infertility, birth defects, developmental delays, early menopause Physical examination o Vital Signs including blood pressure and BMI o Evaluate for thyromegaly, signs of androgen excess (cystic acne, hirsutism, male pattern baldness), skin changes (acanthosis nigricans) o Abdominal Exam with assessment of obesity and presence of abdominal scars o Pelvic examination  Examine for signs of cervicitis (mucopurulent discharge, cervical motion tenderness)  Uterine size, shape, position, mobility  Adnexal masses  Cul-de-sac masses, nodularity, tenderness on exam  Vaginal or cervical structural abnormalities Diagnostic evaluation (see o Ovulatory function  Clinically, if the patient is having regular cycles, particularly if she is having molimina symptoms prior to menses, the patient is most likely ovulatory.  Labs to order: Mid luteal phase serum progesterone level (collected approximately 1wk before anticipated menses, typically day 21 in women with regular cycles).  Home ovulation predictor kits (OPK) can also detect the luteinizing hormone (LH) surge, which occurs just before ovulation. o Ovarian reserve  Labs to order: Anti-mullerian hormone (AMH), Day 3 Follicle stimulating hormone (FSH), Estradiol (E2) AMH is produced by the granulosa cells of the ovary and reflects the primordial follicle pool. It can be obtained at any point in the menstrual cycle.  Antral follicle count Assessed with transvaginal ultrasound. Count follicles measuring 2-10mm in mean diameter. o Tubal patency  Hysterosalpingogram (HSG). Performed cycle day 6-12 when endometrial lining is thin Non-spillage may be due to tubal blockage or due to tubal spasm/myometrial contraction (particularly if proximal tubal occlusion is seen) Diagnostic HSG also has a therapeutic effect – pregnancy rates higher among women after HSG Laparoscopy with chromopertubation Not considered part of initial infertility evaluation. May consider if there is concern for pelvic adhesions or endometriosis o Uterine cavity  HSG can provide information about uterine cavity but has low sensitivity for endometrial polyps and submucosal leiomyomas  Saline-infusion sonohysterography (SHG) is better for identifying intrauterine pathology  Hysteroscopy can be both diagnostic and therapeutic methodology o Additional tests:  Thyroid studies  Prolactin  Fragile X mutation  Karyotype  Androgen profile including testosterone, 17α-hydroxyprogesterone (screening for late onset congenital adrenal hyperplasia), dehydroepiandrosterone sulfate (DHEAS, screening for adrenal abnormality)  Glucose tolerance test, lipid profile for patients with evidence of PCOS  Consider Vitamin D levels Table 1. Diagnostic Assessment for Infertility Clinical Laboratory Additional Testing evaluation Evaluation Ovulatory Regular cycles Day 21 Progesterone Ovulation Predictor Function with molimina (mid luteal phase) Kits (assess for LH symptoms surge) Ovarian AMH Reserve Day 3 FSH and Estradiol (E2) Tubal Patency Hysterosalpingogram (HSG) Uterine Cavity HSG SHG Hysteroscopy Additional Thyroid studies Semen Analysis in assessments Prolactin Male partner Fragile X Additional Testing in Karyotype Male partner as 17α- clinically indicated hydroxyprogesterone DHEAS Glucose tolerance test Lipid profile Vitamin D Male patient Relevant history o Any previous children, previous fertility assessments o Timing and onset of puberty o Medical comorbidities o History of head or pelvic trauma o History of mumps o Previous surgeries to the inguinal or scrotal areas. o Sexual function (assessment of libido, frequency of intercourse)  o Sexually transmitted infection history o Environmental or chemical exposures o Tobacco, illicit drug, alcohol, or exogenous androgen use o Family history of infertility, birth defects, developmental delays, early menopause Physical exam o Body mass index o Signs of endocrinopathies (for example, thyroid dysfunction, Cushing’s syndrome) o Findings of androgen deficiency (loss of secondary sex characteristics) o Genital exam for evidence of incomplete pubertal development Diagnostic evaluation o Semen analysis: Assesses semen volume, sperm concentration, count, motility, and morphology o Additional work up should be referred to a specialist in male infertility Essential Orders Order Day 3 FSH (and/or AMH) E2, PRL, TSH, HSG, Semen analysis, +/- HSG as part of the standard infertility work up LEVEL 3: FORMULATES MANAGEMENT PLANS AND INITIATES TREATMENT FOR COMPLEX AMBULATORY GYNECOLOGIC PROBLEMS. Interpretation: Mid luteal phase (day 21) progesterone: >3 ng/mL suggests recent ovulation FSH and E2 o FSH: will be elevated in women with a reduced follicle pool because more stimulation is required to cause production of ovarian hormones.  A normal FSH is not useful for predicting fertility, but a highly abnormal level (FSH > 20 IU/L) suggests that spontaneous pregnancy is unlikely. 