Snapshot A 35-year-old G1P0 female presents with difficulty becoming pregnant. She and her husband have been trying to conceive for over 12 months, but have been unsuccessful. She reports menarche at age 15 and has had regular periods since then. Her past medical history includes an abortion at age 20 with dilation and curretage procedure. She has also had pelvic inflammatory disorder, treated successfully with antibiotics. SUmmary Inability to conceive after 1 year of unprotected sex in the absence of any known causes of infertility after 6 months if the woman is > 35 years of age or in couples with known risk factors for infertility DisordersCategoryOvulationTubalUterinePathogenesisOvaries fail to produce mature oocyte on a regular basisFallopian tubes fail to capture ovulated ova and/or transport sperm and embryoUterus fails to allow embryo to implant or support growth/developmentRisk factorsIncreasing ageCytotoxic chemotherapyRadiation therapyDiminished ovarian reserveSmokingEndocrine disordershypothalamic amenorrheaPelvic inflammatory diseasetubal inflammationespecially secondary to salpingitis (Gonorrhea/ Chlamydia)Pelvic tuberculosisPelvic surgeryComplicated abdominal surgeryEctopic pregnancyUterine leiomyomaUterine polypsEtiologiesPrimary ovarian insufficiency> 35-years-oldEndocrine disordershypothalamic amenorrheahyperprolactinemiaadrenal diseasepituitary tumorPolycystic ovarian syndromeTurner syndromeAsherman's syndromeintrauterine adhesions result from scar formation after uterine surgeryafter dilation and curettageUterine growths (leiomyoma, polyps)Congenital uterine anomalyseptate uterusunicornate uterusbicornate uterusT-shaped uterusTreatmentOvulation inductionOocyte donationDopamine agonists for hyperprolactinemiaAssisted reproductive technologyTubal microsurgeryLabaroscopic tubal surgeryAssisted reproductive technologySurgeryAssisted reproductive technology Epidemiology 10-15% of reproductive-aged couples in the US More common in developing countries ETIOLOGY Ovulatory disorder Tubal disease Uterine or cervical disorders Endometriosis Idiopathic or advanced maternal age (decreased ovarian reserve) Hypogonadotropic hypogonadism Presentation Symptoms - etiology dependent and thus patients may report hot flashes chronic pelvic or abdominal pain irregularity of menstrual cycle decreased libido history of chemotherapy or radiation therapy history of endometriosis history of pelvic inflammatory disease psychological distress eating disorder Physical exam - etiology dependent and thus one may find body habitus body mass index > 25 kg/m2 or < 17 kg/m2 note, both extremes have been associated with infertility short, stocky, or square-shaped chest may suggest Turner syndrome excessive hair growth acne galactorrhea thyromegaly pelvic exam immobile or mobile uterus discharge from cervix tenderness STUDIES Further testing for female infertility ovulatory function mid-luteal phase serum progesterone level > 3 ng/mL = recent ovulation if < 3 ng/mL, evaluate for causes of anovulation serum prolactin, thyroid-stimulating hormone, and follicle-stimulating hormone (FSH) assess for polycystic ovarian syndrome (PCOS) over the counter urinrary ovulation prediction kit detects leutinizing hormone (LH) 5-10% false positive and false negative rate can detect LH surge, which indicates ovulation ovarian reserve diminished oocyte quality, oocyte quantity, or reproductive potential test ovarian reserve with a day 3 (of menstrual cycle) FSH and estradiol levels other tests clomiphene citrate challenge test provocative test for measurement of FSH anti-Müllerian hormone biochemical marker of ovarian function declines as follicle pool declines fallopian tube patency hysterosalpingogram (HSG) - first-line tubal occlusion or anatomic abnormality unless laparoscopy is planned uterine cavity saline infusion sonohysterography - preferred unless HSG already being done better for diagnosing intrauterine adhesions, polyps, and congenital anomalies hysterosalpingography hysteroscopy - definitive method to evaluate abnormalities of uterine cavity also offers opportunity for treatment at the time of diagnosis. Differential Diagnosis Use of contraception Insufficient time to conceive Male infertility DIAGNOSIS Typically based on history and physical both members of the couple must be evaluated generally start with the male and perform a sperm count Treatment Depends on the cause of infertility (see chart above) Ovulation induction weight change (either lose or gain weight) clomiphene citrate or other selective estrogen receptor modulator (SERM) metformin for PCOS gonadotropins aromatase inhibitors Oocyte donation for primary ovarian insufficiency Assisted reproductive technology in vitro fertilization intrauterine insemination Surgery to correct anatomic abnormality, obstruction, and endometriosis Complications Psychiatric complications depression anxiety sexual dysfunction Prognosis Better chance of fertility with < 32-year-old women presence of ovulatory cycle normal TSH normal levels of anti-müllerian hormone General treatment efficacy 50% pregnancy rate following treatment for infertility best success with ovulatory dysfunction causing infertility less success with severe endometriosis