1. Define infertility and recognize causes of infertility.

2. Determine when to initiate an infertility evaluation.

3. Implement an office-based infertility evaluation.

4. Discuss complications caused by adhesions.

5. Implement surgical strategies that reduce the risk for adhesion formation.

Infertility: Applying New Developments to Office Practice
Michael S. Policar, MD, MPH, Associate Clinical Professor of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, School of Medicine, and Medical Director, California Family Planning Access Care and Treatment (PACT) Program, San Francisco

General considerations: trends affecting infertility services—development of assisted reproductive technologies (ARTs); more women attempting pregnancy later in reproductive years (patient generally older, nulliparous, married, affluent, and insured); infertile couples more likely to seek medical care for infertility; advances in management— less concern with cervical factor as cause of infertility (treated with intrauterine insemination [IUI]); less surgery being performed for tubal factor; surgery of vas deferens replaced by intracytoplasmic sperm injection (ICSI); referral issues—set referral point based on expertise and explain to patient in advance; benefits of relationship with ART provider—avoids duplication of tests; allows for consultations during work-up; provides clear referral threshold points; allows for continuity of care; definition—infertility defined as no pregnancy after 12 months of unprotected intercourse; thresholds for starting infertility work-up in women—<35 yr of age, after 12 mo of unprotected intercourse; 35 to 39 yr of age, at ≈6 mo; 40 yr of age, at 3 mo (some guidelines state 3 mo, others recommend no delay because of decreased likelihood of fertility in older women); after 6 cycles of insemination; work-up should not be delayed in women with history of risk factors for infertility; ≈50% of couples starting infertility services become pregnant on their own

Causes: male factor (≈33% of cases); tubal and peritoneal factors (33%); ovulatory factor, unexplained, and unusual causes (33%); tubal/peritoneal factor—blocked fallopian tubes as result of pelvic inflammatory disease (PID); no history of PID in 50% of women with tubal infertility; peritoneal adhesions; endometriosis; surgical treatment superior to medical treatment at improving fertility; ovulatory factors—anovulation; luteal phase insufficiency; poor quality ovulation (ie, poor ovarian reserve); cervical factor—“hostile” or scant mucus (hypoestrogenic effect); prevention—annual Chlamydia screening in women <26 yr of age; targeted screening in patients engaging in risky behaviors; patients engaging in risky behaviors should use barrier contraception in addition to other contraceptive method; use of hormonal contraceptives to avoid ectopic pregnancy and endometriosis (ovulation less likely with extended methods); early childbearing for prevention of ovulatory factor infertility; men should undergo Chlamydia screening to prevent epididymitis

Age and fertility: starting at 30 yr of age, women have more ovulation and peritoneal-factor infertility; higher miscarriage rates; more pregnancy-related maternal conditions; higher rates of congenital anomalies; approximately one-third of women in their mid or late 30s have fertility problems; 50% of women ≥40 yr of age have problems; in women ≥40 yr of age, likelihood of success with IVF 5% per cycle and <10% with multiple cycles; better success with donor eggs from younger women; aging and reproduction—highest fertility in women until late 20s; decreases to ≈60% of baseline by time women in early 30s; 80% of baseline by late 30s; miscarriage—inflection point at mid 30s, increases thereafter

Male partner’s work-up: history that suggests work-up appropriate—fathered previous pregnancies within 3 yr; genital trauma or surgery; genital infections; environmental heat (eg, spas, tight pants, extended time sitting); coital frequency and technique; current exposures to drugs (eg, \89 β-blockers, calcium channel blockers, cimetidine, statins), toxic chemicals (eg, metals, dyes); recreational drug and alcohol use and cigarette smoking; examination— preferable, but little contribution if semen analysis normal; presence of masculine traits reflective of amount of testosterone from testicles; varicocele may increase likelihood of problem with spermatogenesis; ejaculatory problems with hypospadias; infection with urethral discharge and prostatitis; laboratory tests—semen analysis (abstain from ejaculation 2-3 days before sampling); check with laboratory for collection protocol

Work-up of woman: history—previous infertility work-up, evaluation, and treatments; PID or pelvic infections; pelvic pain and dysmenorrhea; endometriosis; diabetes or thyroid disease; cigarette smoking (negative impact on fertility in men and women); galactorrhea; menstrual patterns (especially if patient having moliminal symptoms; examination—body mass index (BMI) >30 (patient more likely to have polycystic ovary syndrome (PCOS), with anovulation being cause of infertility); hirsutism, acne, male-pattern balding; galactorrhea (work-up for prolactinemia warranted); cervical infection; bimanual examination of uterus, fallopian tubes, and ovaries; laboratory tests— complete blood cell count (CBC); erythrocyte sedimentation rate (ESR); thyroid hormone and prolactin levels; ovarian reserve testing if indicated; gonorrhea and Chlamydia screening if indicated; microscopy of cervical mucus (cervical inflammation cause of cervical factor infertility); diagnostic pelvic ultrasonography (US) useful in diagnosing PCOS, endometriosis, and ovarian volume

Counseling issues: timing of intercourse (just before ovulation [subtract 14 days from usual cycle length] recommended); use of ovulation prediction kit; coital frequency and technique; intercourse starting 4 to 5 days before expected ovulation; woman should lay supine with knees up for at least 10 to 15 min after intercourse; avoid sperm-toxic lubricants (vegetable oil can be used); smoking cessation (both partners); weight loss if woman’s BMI ≥30; preconception care—folic acid 400 µg daily; rubella serology (immunize if seronegative); change medications to those in safer pregnancy category; blood glucose control if woman has diabetes; semen analysis—man considered fertile if >20 million sperm/mL; repeat in 10 wk if oligospermia found; refer man with 2 consecutive low semen analyses to urologist for work-up

Documenting ovulation: ways to confirm ovulation—menstrual calendar; mid luteal phase progesterone (9 ng/mL); ovulation prediction kit; pelvic US evidence of ovulation; endometrial biopsy and basal body temperature elevation outdated indicators; ovulation prediction kits—positive with luteinizing hormone (LH) surge; test positive 24 to 36 hr before ovulation; positive test indicates presence of ovulation and ideal timing for intercourse; 5 to 9 urine dipsticks; perform on late afternoon urine sample; start testing 3 or 4 days before expected ovulation; day of or day after positive test best time for intercourse; indications for ovarian reserve testing—patient 30 to 40 yr of age; unexplained infertility; poor response to clomiphene; family history of early menopause; cigarette smoking; previous ovarian surgery; single day-3 follicle-stimulating hormone (FSH) level >10 to 15 mIU/mL considered abnormal

Follow-up: if patient appears ovulatory, proceed to hysterosalpingography (HSG); if anovulatory, induce ovulation; anovulation presentations—oligomenorrhea or amenorrhea or dysfunctional uterine bleeding; absence of moliminal symptoms; short or long menstrual cycle; previous need for ovulation induction; physical findings of PCOS; interventions for anovulation—induce menses with medroxyprogesterone acetate (MPA) or micronized progesterone; first day of bleeding considered day 1; start clomiphene on day 3, 4, or 5; start with clomiphene 50 mg once daily for 5 days; average woman ovulates 5 to 7 days after last clomiphene tablet; start ovulation prediction testing 4 days after last clomiphene dose; increase clomiphene to 100 to 150 mg if ovulation does not occur; if patient still not ovulating, prescribe metformin alone for 8 to 12 wk, then metformin daily and clomiphene for 5 days during cycle; data show metformin alone not as effective as clomiphene alone and clomiphene alone almost as effective as clomiphene plus metformin; postcoital test—evidence does not support use; data show slightly higher fertility rates in women who used nonspermicidal vaginal moisturizer (helps sperm motility), compared to those who did not; IUI—used in cases of low sperm counts and cervical factor infertility; seminal fluid placed into uterus, bypassing cervix entirely; evaluating uterine and tubal factors—if fallopian tubes not blocked, timed intercourse for ≥3 mo; if blocked, refer for ART; laparoscopy last step to assess for internal evidence of endometriosis or blocked fallopian tubes; conditions warranting direct referral for ART—patient in her late 30s to 40s; infertility ≥3 yr; documented anatomic defect; major medical condition; severe endometriosis; unexplained infertility (not responsive to treatment)

Evaluation algorithm: high-risk factors—refer directly for ART; no high-risk factors—determine ovulation status and check day-3 FSH; perform HSG if patient ovulatory; if patient anovulatory—induce 4 ovulatory cycles; refer for ART if pregnancy does not occur or patient has poor ovarian reserve; if patient ovulatory and HSG normal—wait 3 to 6 mo; if concerned about endometriosis, perform laparoscopy; if no concern about endometriosis, case categorized as unexplained infertility; last step—combination of IUI and ovulation induction; if patient still not pregnant, refer for ART

Adhesions in Gynecologic Surgery: How to Handle and Prevent
Peter Takacs, MD, PhD, Associate Professor, Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, University of Miami, Miller School of Medicine, Miami, FL

Introduction: postsurgical adhesions occur in ≈70% to 95% of patients undergoing major gynecologic surgery; most abdominal adhesions asymptomatic; 4% of patients undergoing abdominal or pelvic surgery readmitted to hospital with adhesion-related complications

Complications: intestinal obstruction; chronic pain; infertility; difficult subsequent surgery; postsurgical adhesions cause >40% of cases of intestinal obstruction and 60% to 70% of cases of small bowel obstruction (SBO); obstruction can occur ≤1 mo to >10 yr after surgery; study showed total abdominal hysterectomy (TAH) most common cause of SBO; median interval between TAH and SBO 4 yr; adhesions adherent to previous laparotomy incision in 75% of cases and to vaginal vault in 25% of cases; peritoneal closure not associated with SBO; infertility—≈15% to 20% of cases of female infertility caused by adhesions; adhesions surrounding ovaries can inhibit follicular growth; peritubal adhesions affect tubal motility and ovum transport; study—found no significant difference between degree of adhesions in women treated by laparotomy and salpingoovariolysis, compared to those untreated; study concluded that although pregnancy might occur in infertile women with periadnexal adhesions, treatment with salpingoovariolysis associated with higher pregnancy rate; study participants followed for average of 49 mo after tubal surgery; term pregnancy rates inversely correlated with adhesion scores (American Society for Reproductive Medicine classification system for adnexal adhesions); pain—adhesions suggested to be most common cause of pelvic and abdominal pain (association controversial); increased tension or stretching of pelvic organs may be mechanism of chronic pelvic pain associated with adhesions; data show that, although laparoscopic adhesiolysis relieves chronic abdominal pain, it is not more beneficial than diagnostic laparoscopy alone; not recommended as treatment for adhesions in patients with chronic abdominal pain

Pathophysiology: formation of adhesions may occur in connective tissue from time of surgery up to 5 days after surgery; fibrin—inadequate breakdown of fibrin causes ingrowth of fibroblasts, capillaries, and nerves, leading to formation of permanent fibrous connective tissue; fibrin breakdown and adhesion formation influenced by genetic polymorphisms (in animals and humans) that affect inflammatory and healing process; initially neutrophils, but predominant cells become macrophages in ≤24 hr; reperitonealization continues for 7 to 10 days; entire surface becomes covered by contiguous sheet of mesothelium (processes markedly different from normal wound healing); speed of reperitonealization remains same, regardless of initial wound size; no adhesion formation with complete fibrinolysis

Management: simple adhesive obstruction resolved without need for further surgical intervention, provided patient in stable condition; SBO—intervention needed when integrity of bowel compromised due to strangulation or infarction; fever, tachycardia, peritonitis, abdominal mass, elevated white blood cells, and toxemia reflect severity of patient’s condition, but not necessarily severity or quantity of adhesions; delay in treatment significantly increases mortality from ≈5% to 30%; infertility and pain—pregnancy rates of 38% to 52% achieved after removal of adhesions in previously infertile women; studies show reduction in pelvic pain associated with adhesions after adhesiolysis in 40% to 90% of patients (however, data show no significant benefit over sham surgery); prevention— laparoscopic approach; minimize tissue necrosis; hemostasis; irrigation (use liberally); nonreactive suture material; reduce extent of trauma through minimal tissue handling; prevent desiccation; ensure optimal temperature of irrigation solutions; reduce foreign material entering abdomen; use powder-free gloves; trials looking at suturing peritoneum in women undergoing cesarean delivery concluded improved short-term postoperative outcome if peritoneum not closed; laparoscopy vs laparotomy—insufflation of abdomen with gas may cause biochemical changes; laparoscopic graspers cause of significant damage to tissue surfaces; mixed results seen in studies comparing adhesion potential of laparoscopy to that of laparotomy; however, laparoscopy appears associated with lower adhesion formation; laparoscopic procedures requiring extended insufflation more likely to result in adhesion formation than shorter procedures; insufflation of CO2 without humidification (dry CO2 ) cause of adhesion formation; level of inflammatory cellular response and mesothelial desquamation shown significantly more pronounced in abdomens of rats exposed to cold and dry rather than warm and humid gas

Barrier drugs: barrier should remain effective for at least 3 to 5 days for mesothelium to be reestablished; expanded polytetrafluoroethylene (Gore-Tex)—nonabsorbable; not widely used; human amniotic membrane (Seprafilm)—hyaluronic acid and carboxymethylcellulose; completely biodegradable; remains effective in presence of blood; ≈40% reduction in adhesion formation; difficult to apply at laparotomy and laparoscopy; possibility of increased risk for embolism or abscess formation reported in some patients; nontoxic; used commonly as filler in food, cosmetics, and pharmaceuticals; hyaluronic acid film transparent and absorbable membrane; acts to separate opposing tissue surfaces; lasts ≈7 days; data show limited evidence for effectiveness in preventing adhesion formation after myomectomy; oxidized regenerated cellulose (Interceed [TC7])—biodegradable membrane; breaks down within 28 days of application; prevents adhesion only if no blood or excess peritoneal fluid present; even small amount of blood able to permeate material, which allows fibroblasts to grow along clotted blood and form adhesions; degraded into monosaccharides and absorbed within 2 wk after application; data show adhesion formation reduced by 50% to 60%; no evidence that reduction in adhesions resulting from use of oxidized regenerated cellulose improves fertility; liquid barriers—antibiotic solutions for peritoneal lavage and prevention of postoperative infection do not reduce adhesions; some may even promote adhesion formation; side effects and inconsistent clinical outcomes have restricted use