Infertility

Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?) Fertility –Ability to conceive Fecundity –Ability to carry to delivery

Statistics 80% of couples will conceive within 1 year of unprotected intercourse ~86% will conceive within 2 years ~14-20% of US couples are infertile by definition (~3 million couples) Origin: –Female factor ~40% –Male factor ~30% –Combined ~30%

Etiologies Sperm disorders 30.6% Anovulation/oligoovulation 30% Tubal disease 16% Unexplained 13.4% Cx factors 5.2% Peritoneal factors 4.8%

Associated Factors PID Endometriosis Ovarian aging Spermatic varicocoele Toxins Previous abdominal surgery (adhesions) Cervical/uterine abnormalities Cervical/uterine surgery Fibroids

Emotional and Educational Needs Disease of couples, not individuals Feelings of guilt Where to go for information? Options Feelings of frustration and anger Support groups (e.g. Resolve)

Overview of Evaluation Female –Ovary –Tube –Corpus –Cervix –Peritoneum Male –Sperm count and function –Ejaculate characteristics, immunology –Anatomic anomalies

History-General Both couples should be present Age Previous pregnancies by each partner Length of time without pregnancy Sexual history –Frequency and timing of intercourse –Use of lubricants –Impotence, anorgasmia, dyspareunia –Contraceptive history

History-Male History of pelvic infection Radiation, toxic exposures (include drugs) Mumps Testicular surgery/injury Excessive heat exposure (spermicidal)

History-Female Previous female pelvic surgery PID Appendicitis IUD use Ectopic pregnancy history DES (?relation to infertility) Endometriosis

History-Female Irregular menses, amenorrhea, detailed menstrual history Vasomotor symptoms Stress Weight changes Exercise Cervical and uterine surgery

Physical Exam-Male Size of testicles Testicular descent Varicocoele Outflow abnormalities (hypospadias, etc)

Physical Exam-Female Pelvic masses Uterosacral nodularity Abdominopelvic tenderness Uterine enlargement Thyroid exam Uterine mobility Cervical abnormalities

Overall Guidelines for Work-up Timeliness of testing-w/u can usually be accomplished in 1-2 cycles Timing of tests Don’t over test Cut to the chase, i.e. proceed with laparoscopy if adhesive disease is likely

Ovarian Function Document ovulation: –BBT –Luteal phase progesterone –LH surge –EMBx If POF suspected, perform FSH TSH, PRL, adrenal functions if indicated The only convincing proof of ovulation is pregnancy

Ovarian Function Three main types of dysfunction –Hypogonadotrophic, hypoestrogenic (central) –Normogonadotrophic, normoestrogenic (e.g. PCOS) –Hypergonadotrophic, hypoestrogenic (POF)

BBT Cheap and easy, but… –Inconsistent results –Provides evidence after the fact (like the old story about the barn door and the horse) –May delay timely diagnosis and treatment –98% of women will ovulate within 3 days of the nadir –Biphasic profiles can also be seen with LUF syndrome

Luteal Phase Progesterone Pulsatile release, thus single level may not be useful unless elevated Performed 7 days after presumptive ovulation Done properly, >15 ng/ml consistent with ovulation

Urinary LH Kits Very sensitive and accurate Positive test precedes ovulation by ~24 hours, so useful for timing intercourse Downside: price, obsession with timing of intercourse

Endometrial Biopsy Invasive, but the only reliable way to diagnose LPD ??Is LPD a genuine disorder??? Pregnancy loss rate <1% Perform around 2 days before expected menstruation (= day 28 by definition) Lag of >2 days is consistent with LPD Must be done in two different cycles to confirm diagnosis of LPD

Tubal Function Evaluate tubal patency whenever there is a history of PID, endometriosis or other adhesiogenic condition Kartagener’s syndrome can be associated with decreased tubal motility Tests –HSG –Laparoscopy –Falloposcopy (not widely available)

Hysterosalpingography (HSG) Radiologic procedure requiring contrast Performed optimally in early proliferative phase (avoids pregnancy) Low risk of PID except if previous history of PID (give prophylactic doxycycline or consider laparoscopy)

Laparoscopy Invasive; requires OR or office setting Can offer diagnosis and treatment in one sitting Not necessary in all patients Uses (examples): –Lysis of adhesions –Diagnosis and excision of endometriosis –Myomectomy –Tubal reconstructive surgery

Uterus Asherman Syndrome –Diagnosis by HSG or hysteroscopy –Usually s/p D+C, myomectomy, other intrauterine surgery –Associated with hypo/amenorrhea, recurrent miscarriage Fibroids, Uterine Anomalies –Rarely associated with infertility –Work-up: Ultrasound Hysteroscopy Laparoscopy

Cervical Function Infection –Ureaplasma suspected Stenosis –S/P LEEP, Cryosurgery, Cone biopsy (probably overstated) Immunologic Factors –Sperm-mucus interaction

Cervical Function Tests: –Culture for suspected pathogens –Postcoital test (PK tests) Scheduled around 1-2d before ovulation (increased estrogen effect) 48 0 of male abstinence before test No lubricants Evaluate 8-12h after coitus (overnight is ok!) Remove mucus from cervix (forceps, syringe)

Peritoneal Factors Endometriosis –2x relative risk of infertility –Diagnosis (and best treatment) by laparoscopy –Etiology unknown but likely multiple ones Retrograde menstruation Immunologic factors Genetics –Medical options remain suboptimal

Male Factors

Serum T, FSH, PRL levels Semen analysis Testicular biopsy Sperm penetration assay (SPA)

Male Factors-Semen Analysis Collected after 48 0 of abstinence Evaluated within one hour of ejaculation If abnormal parameters, repeat twice, 2 weeks apart

Normal Semen Analysis

Treatment Options

Ovarian Disorders Anovulation –Clomiphene Citrate ± hCG –hMG –Induction + IUI (often done but unjustified) PRL –Bromocriptine –TSS if macroadenoma POF –?high-dose hMG (not very effective)

Ovarian Disorders Central amenorrhea –CC first, then hMG –Pulsatile GnRH LPD –Progesterone suppositories during luteal phase –CC ± hCG

Ovarian Matrix

Ovulation Induction CC –70% induction rate, ~40% pregnancy rate –Patients should typically be normoestrogenic –Induce menses and start on day 5 –With dosages, antiestrogen effects dominate –Multifetal rates 5-10% –Monitor effects with PK, pelvic exam

hMG (Pergonal) LH +FSH (also FSH alone = Metrodin) For patients with hypogonadotrophic hypoestrogenism or normal FSH and E 2 levels Close monitoring essential, including estradiol levels 60-80% pregnancy rates overall, lower for PCOS patients 10-15% multifetal pregnancy rate

Risks CC Vasomotor symptoms H/A Ovarian enlargement Multiple gestation NO risk of SAb or malformations hMG Multiple gestation OHSS (~1%) –Can often be managed as outpatient –Diuresis –Severe cases fatal if untreated in ICU setting

Fallopian Tubes Tuboplasty IVF GIFT, ZIFT not options

Corpus Asherman syndrome –Hysteroscopic lysis of adhesions (scissor) –Postop Abx, E 2 Fibroids (rarely need treatment) –Myomectomy(hysteroscopic, laparoscopic, open) –??UAE Uterine anomalies (rarely need treatment) –metroplasty

Peritoneum (Endometriosis) From a fertility standpoint, excision beats medical management Lysis of adhesions GnRH-a (not a cure and has side effects, expense) Continuous OCP’s (poor fertility rates) Chances of pregnancy highest within 6 mos-1 year after treatment

Male Factor Hypogonadotrophism –hMG –GnRH –CC, hCG results poor Varicocoele –Ligation? (no definitive data yet) Retrograde ejaculation –Ephedrine, imipramine –AIH with recovered sperm

Male Factor Idiopathic oligospermia –No effective treatment –?IVF –donor insemination

Unexplained Infertility 5-10% of couples Consider PRL, laparoscopy, other hormonal tests, cultures, ASA testing, SPA if not done Review previous tests for validity Empiric treatment: –Ovulation induction –Abx –IUI –Consider IVF and its variants Adoption

Summary Infertility is a common problem Infertility is a disease of couples Evaluation must be thorough, but individualized Treatment is available, including IVF, but can be expensive, invasive, and of limited efficacy in some cases Consultation with a BC/BE reproductive endocrinologist is advisable