INTRODUCTION — Infertility is a complex disorder with significant medical, psychosocial, and economic aspects. While great strides have been achieved in infertility therapy, evidence-based studies have questioned the validity of historically accepted tests for its diagnosis.
The evaluation of female infertility will be reviewed here. The etiology and treatment of female infertility are discussed separately. (See "Etiology of female infertility" and "Overview of treatment of female infertility".)
PROVIDER — Most infertility evaluations should be directed by fertility specialists or physicians with experience in the evaluation and treatment of infertility [1-3]. Guidelines for practices offering assisted reproductive technologies have been developed by the American Society for Reproductive Medicine [4].
TIMING — The general consensus is that infertility evaluation should be undertaken for couples who have not been able to conceive after 12 months of unprotected and frequent intercourse, but earlier evaluation can be justified based on medical history and physical findings, and in women over 35 years of age [5,6]. Some authorities have proposed initiating an infertility workup after six months of fertility-oriented intercourse without conception since prospective cohort studies have shown that a significant decline in fecundity occurs by this time (table 1) [7-9].
The timing of initial evaluation of infertility depends upon the age of the female partner, as well as the couple's historical risk factors (table 2). Women experience a decline in fecundity due to ovarian aging, which correlates with increased chronological age [10]. Thus, delaying evaluation and treatment of a woman in her mid-thirties may result in lower success rates once therapy is initiated (graph 1).
In light of these data, we suggest immediate evaluation in women over 40 years of age. In women between 35 and 40 years of age, we initiate evaluation after six months of unprotected intercourse without conception. Evaluation is initiated sooner if the female partner has a history of oligomenorrhea/amenorrhea, pelvic infection or surgery, chemotherapy and/or radiation, or endometriosis [11]. Male factors can also be indications for initiating early evaluation of the male partner. These factors include a history of testicular trauma requiring treatment, adult mumps, impotence or other sexual dysfunction, chemotherapy and/or radiation, or a history of subfertility with another partner.
For younger couples, we suggest focusing the initial intervention on teaching timed intercourse with the aid of a urinary ovulation predictor kit, and advising at least 12 months of attempts at conception before initiating the infertility evaluation. In addition, changes in lifestyle factors that may improve fertility should be recommended, including achieving an ideal body mass index, cessation of smoking, and limiting exposure to caffeine and alcohol. However, evaluation is initiated sooner if the female partner has a history of oligomenorrhea/amenorrhea, pelvic infection or surgery, chemotherapy and/or radiation, or endometriosis or male risk factors are present. (See "Optimizing natural fertility in couples planning pregnancy".)
HISTORY AND PHYSICAL EXAMINATION — Components of the infertility history are listed in the table (table 2). The most important points in the history are:
- Duration of infertility and results of previous evaluations and therapy
- Menstrual history to help determine ovulatory status
- Medical, surgical, gynecological, and obstetrical history to determine whether there are disorders and medications associated with infertility
- Sexual history, including sexual dysfunction and frequency of coitus
- Personal and life-style history including age, occupation, exercise, stress, dieting, smoking, and alcohol use, all of which can affect fertility
Physical examination should include calculation of the patient's body mass index (BMI) and assessment for signs of potential causes of infertility: abnormalities of the thyroid gland; galactorrhea; signs of androgen excess (hirsutism, acne, male pattern baldness); tenderness or masses in the adnexae or posterior cul-de-sac (pouch of Douglas); vaginal/cervical abnormalities; and uterine enlargement, irregularity, or lack of mobility [11].
BASIC EVALUATION — It is important to remember that the couple may have multiple factors contributing to their infertility; therefore, a complete basic evaluation needs to be performed. Basic testing in the initial evaluation consists of:
- Semen analysis to detect male factor infertility
- Documentation of normal ovulation by history and midluteal serum progesterone level
- Hysterosalpingogram (HSG) to rule out tubal occlusion
Risk factors noted from the couple's history may indicate the need for additional testing after the initial infertility consultation. Preconceptional laboratory assessment may also be undertaken at this time so these results can be considered in diagnostic and therapeutic counseling. (See "Preconception evaluation and counseling".)
Semen analysis — The semen sample should be collected after two to seven days of abstinence and should be given to the laboratory within one hour of collection [12]. It is difficult to predict likelihood of pregnancy based upon the semen analysis alone as there is extensive overlap between the semen parameters of fertile and infertile men. If the semen analysis is abnormal, the clinician should review details of specimen collection and transport with the patient, repeat the test due to the marked inherent variability of semen analyses, and then consider referral to a urologist. A variety of techniques for semen analysis and interpretation of results are discussed in detail separately. (See "Evaluation of male infertility", section on 'Standard semen analysis'.)
Assessment of ovulatory function — Women with a history of regular menstrual cycles (ie, every 25 to 35 days) and moliminal symptoms (eg, breast tenderness) do not require laboratory confirmation of ovulation [13]. Tests that assess ovarian reserve are not useful for predicting pregnancy in this population.
Women with irregular cycles — If the woman's menstrual cycles are not regular, we suggest evaluating for ovulation by having the patient use an over-the-counter urinary luteinizing hormone (LH) kit to detect LH surge or by obtaining a midluteal serum progesterone level. We obtain a midluteal serum progesterone level 18 to 24 days after the onset of menses; a value greater than 3 ng/mL is diagnostic of ovulation. We prefer the serum test because it is not subject to observer misinterpretation as with home urine tests, which have a 5 to 10 percent false positive rate. (See "Evaluation of the menstrual cycle and timing of ovulation", section on 'Measurement of LH surge'.)
This approach is useful in women with slightly extended cycle lengths (eg, 35 to 45 days between cycles). For women with more severe oligomenorrhea (eg, more than 45 days between cycles) it is unlikely that trying to measure LH or luteal progesterone will provide useful information or markedly alter therapy. In these cases, we look for the cause of the oligomenorrhea and move on to treatment.
The underlying cause of ovulatory dysfunction should be determined (table 3), when possible, as treatment of the specific abnormality may result in return of ovulation. In addition, the optimal treatment of infertility is often determined by the underlying cause.
Amenorrheic women — In amenorrheic women (after pregnancy has been excluded), a progestin challenge test should be utilized to verify ovarian estradiol production and the presence of a normal outflow tract. A progestin (eg, medroxyprogesterone acetate 10 mg/day orally for five days or progesterone 100 mg intramuscularly in oil) is administered; bleeding in the week after the challenge indicates that adequate estrogen is present to impact the endometrium and that a patent outflow tract exists. If a withdrawal bleed does not occur, then the outflow tract should be evaluated with ultrasound (or magnetic resonance imaging if ultrasound is not definitive) and, if an outflow tract is present, the patient should be evaluated for ovarian failure (see 'Assessment of ovarian reserve' below) and for hypothalamic dysfunction. (See "Etiology, diagnosis, and treatment of primary amenorrhea" and "Etiology, diagnosis, and treatment of secondary amenorrhea".)
Assessment of fallopian tube patency
Hysterosalpingogram — We obtain a hysterosalpingogram (HSG) on all patients in whom laparoscopy is not planned to look for tubal occlusion and evaluate the uterine cavity [14,15]. Either water or lipid soluble contrast media can be used. (See "Hysterosalpingography".)
A meta-analysis of 20 studies involving 4179 patients compared HSG and laparoscopy with chromopertubation (the gold standard) and concluded that the high specificity of the HSG (83 percent) makes it useful for confirming tubal patency [14]. However, HSG was not very sensitive (65 percent) for diagnosing tubal occlusion due to a high false positive rate. Furthermore, it was not reliable in the evaluation of peritubal adhesions or endometriosis.
When subgroups of women undergoing HSG were analyzed, HSG appeared to have very high specificity and sensitivity for diagnosing 'distal' tubal occlusion or major 'distal' tubal adhesions, but much lower specificity for diagnosing 'proximal' tubal occlusion.
Given these deficiencies, findings of proximal tubal occlusion on HSG should be confirmed by a secondary test such as a tubal catheter salpingogram (using interventional radiology), if indicated. We perform laparoscopy (diagnostic, therapeutic) in women with suspected endometriosis or pelvic adhesions. (See 'Diagnostic laparoscopy' below.)
Diagnostic HSG may also have therapeutic effects. Several studies have reported increased pregnancy rates after diagnostic hysterosalpingography. The value of this technique was illustrated in a systematic review of 12 randomized trials [16]. The major findings from this analysis were:
- Tubal flushing with oil-soluble media (eg, lipiodol) versus no intervention was associated with a significant increase in pregnancy rate (OR 3.30, 95% CI 2.00-5.43)
- Tubal flushing with oil-soluble media was not significantly more effective than tubal flushing with water-soluble media for achieving pregnancy (OR 1.21, 95%CI 0.95-1.54).
- The addition of oil-soluble media to flushing with water-soluble media (water-soluble plus oil-soluble media versus water-soluble media alone) also did not show a significant benefit for achieving pregnancy (OR 1.28, 95% CI 0.92-1.79).
Chlamydia antibodies — Chlamydia trachomatis antibody testing is a simple, inexpensive, and noninvasive test with some evidence supporting its use as a method for predicting the presence of tubal disease. Studies suggest that the presence of antibodies to chlamydia are more predictive of infertility than an abnormal HSG or a history of previous use of a copper IUC [17-20]. Multiple tests are available [21], but not widely utilized given only limited data supporting their use. A cost-effective approach might be to screen women at low risk of tubal disease with chlamydia antibodies and screen women at high risk of tubal disease with an immediate HSG [22]. Women with positive chlamydia antibodies would then have an HSG. This test may also be utilized in women with an allergy to shellfish or iodinated contrast agents who cannot undergo an HSG
FOLLOW-UP EVALUATION
Assessment of ovarian reserve — Ovarian reserve is assessed in women over 35 years of age and younger women with risk factors for premature ovarian failure (previous extensive ovarian surgery, exposure to cytotoxic drugs or pelvic radiation therapy, autoimmune disease, smokers, strong family history of early menopause/premature ovarian failure). (See "Pathogenesis and causes of spontaneous premature ovarian failure" and "Ovarian failure due to anticancer drugs and radiation" and "Pathogenesis, diagnosis, and treatment of autoimmune ovarian failure".)
Identification of depleted ovarian reserve is the goal of a number of tests, including:
- Day 3 FSH concentration
- Clomiphene citrate challenge test (CCCT) (oral administration of 100 mg clomiphene citrate on cycle days 5 through 9 with measurement of day 3 and day 10 FSH levels and day 3 estradiol level)
- Ultrasound imaging of the ovary to determine either ovarian volume and/or antral follicle count
- Day 3 inhibin-B
- Anti-mullerian hormone (AMH) level
- GnRH agonist stimulation.
In a population of women, these markers predict the quality and number of oocytes in the ovary, and hence their prognosis for becoming pregnant, either spontaneously or with assisted reproductive technologies (ART). However, for any given woman, they are not highly accurate, raising the ethical problem of whether women should be denied infertility treatment if one of these tests of ovarian function is abnormal.
Day 3 FSH and CCCT — The most widely used tests for assessment for ovarian reserve are the day 3 FSH level and the CCCT, which is a provocative test for measurement of FSH. The basis of these tests is that women with good ovarian reserve have sufficient production of ovarian hormones early in the menstrual cycle to maintain FSH at a low level. In contrast, women with a reduced pool of oocytes and poor oocyte quality have insufficient production of ovarian hormones to provide normal inhibition of pituitary secretion of FSH, so FSH rises early in the cycle [23].
The value of these tests was illustrated by the following meta-analyses:
- A meta-analysis of 19 published studies evaluated either basal FSH level or the CCCT for predicting treatment outcome in an infertility clinic population [24]. Both tests were similar in predicting achievement of pregnancy in women undergoing infertility treatment: while a normal result was not useful (many infertile women had normal tests), an abnormal result with either test virtually confirmed that pregnancy would not occur with treatment. Unfortunately, few infertile women had FSH levels high enough to be considered abnormal. Combining a basal estradiol level with FSH measurement on day 3 improved the sensitivity in patients undergoing IVF [25].
- Another meta-analysis of FSH and CCCT testing, which used failure to become pregnant after IVF as the outcome measure, came to a similar conclusion [26].
- A third meta-analysis concluded variations in definitions and selection bias precluded a definitive recommendation, but the CCCT appeared to have no advantage over basal FSH measurement for assessing ovarian reserve [27].
Based on these findings, we obtain a cycle day 3 FSH concentration and consider a value less than 15 mIU/mL suggestive of adequate ovarian reserve. Typically, levels of 10 to 15 mIU/ml are considered borderline. The upper threshold for a normal FSH concentration is laboratory dependent; cutoff values of 10 to 25 mIU/mL have been reported because of use of different FSH assay reference standards. Since there is no absolute threshold between normal and abnormal, values that are neither very low nor very high are not highly predictive of ovarian reserve. Furthermore, measurement of FSH in a single cycle may not be sufficient since concentrations fluctuate from cycle to cycle: a normal result in one cycle may be abnormal if repeated in a subsequent cycle; however, even one abnormal result suggests diminished ovarian reserve.
We also check a cycle day 3 estradiol level, although there are conflicting data as to whether it is predictive of ovarian reserve and the response to ovarian stimulation (as in IVF). Elevated basal estradiol levels are due to rapid premature follicle recruitment, which occurs in women with poor ovarian reserve. High estradiol levels can inhibit pituitary FSH production and thus mask one of the signs of decreased ovarian reserve in perimenopausal women. Thus, measurement of both FSH and estradiol levels helps avoid false-negative FSH testing.
If CCCT is performed, we consider a FSH less than 15 mIU/mL on both day 3 and day 10 normal; an elevated FSH level on either day 3 or day 10 is suggestive of decreased ovarian reserve. Estradiol can be measured on day 3, but is not measured on day 10 because an elevated level at that time is a normal result of clomiphene citrate administration.
GnRH agonist stimulation test — The GnRH agonist stimulation test is a similar type of test, but offers no advantage to the above, simpler tests [28,29]. Disadvantages of this test are that it requires an injection and venipuncture for timed samples.
Ovarian volume and antral follicle count — Ultrasound examination can be used to determine mean ovarian volume and the number of antral follicles. A study comparing the ability of ovarian reserve tests to predict ovarian response and pregnancy concluded that sonographically measured ovarian volume and an abnormal CCCT were better than other hormonal and sonographic tests in predicting the response to ovarian stimulation in IVF cycles [30]. In this study, however, age was the only independent predictor of pregnancy in IVF as compared to hormonal and ultrasound indices of ovarian reserve.
On transvaginal ultrasound, the presence of at least 5 to 10 antral follicles measuring between 2 and 10 mm in diameter suggests good ovarian reserve [31,32]. Two studies demonstrated that low antral follicle counts were predictive of poor ovarian response in IVF, but did not predict pregnancy, even in combination with other ovarian reserve factors [31,32]. We do not obtain this test since it requires an ultrasonographer experienced in obtaining antral follicle counts, but other centers find it useful.
Inhibin B — Inhibin-B levels fall in women with decreased ovarian reserve prior to the elevation in FSH levels [33], prompting investigations into the potential of inhibin-B as a direct marker of ovarian reserve. One study demonstrated that women with low day 3 serum inhibin-B concentrations had a poorer response to ovulation induction and were less likely to conceive through ART relative to women with a high day 3 inhibin-B [34]. Other studies, however, have failed to show inhibin-B to be predictive of pregnancy in women undergoing infertility or ART therapies [35,36]. Moreover, there is no accepted international standard for the inhibin-B assay, making correlation between laboratories difficult. We do not order this test due to laboratory variability.
Anti-müllerian hormone — Anti-müllerian hormone (AMH) is a member of the TGF-beta family and is expressed by the small (<8 mm) preantral and early antral follicles. The AMH level reflects the size of the primordial follicle pool. In adult women, AMH levels gradually decline as the primordial follicle pool declines with age and the AMH level appears to be an early, reliable, direct indicator of declining ovarian function. A serum AMH level above 0.7 ng/mL is consistent with good ovarian reserve, while lower levels suggest the presence of a depleted ovarian follicle pool. AMH is undetectable at menopause [37]. AMH may play an especially useful role in identifying reduced ovarian follicle pool in certain types of patients, such as cancer patients [38].
AMH can be measured anytime during the menstrual cycle and typically demonstrates minimal intercycle and intracycle variability since the growth of small preantral follicles that express it is continuous, not cyclical. AMH kits are readily available from multiple vendors and AMH measurements can be obtained from large clinical reference laboratories [39,40], but most insurers in the United States do not reimburse for the test. The lack of reimbursement makes its use problematic. AMH is being used actively in Europe [41].
Assessment of the uterine cavity — HSG may identify abnormalities of the uterine cavity with potential affects on fertility, such as submucous fibroids, a T-shaped cavity (associated with DES exposure), polyps, synechiae, and congenital müllerian anomalies (although HSG alone cannot reliably distinguish between a uterine septum or bicornuate uterus).
Abnormalities found on HSG generally require further evaluation by laparoscopy, hysteroscopy, or other imaging modalities (ultrasonography or magnetic resonance imaging). Ultrasonography is a useful test for evaluation of suspected leiomyoma, while saline infusion sonohysterography is the best imaging modality for assessment of submucosal leiomyoma and is much better than routine ultrasonography for diagnosis of intrauterine adhesions and congenital uterine anomalies [42]. Hysteroscopy is the definitive method for evaluation of abnormalities of the endometrial cavity, and can sometimes be employed for their treatment as well. Evaluation of uterine anomalies depends on the anomaly and is discussed separately. (See "Overview of hysteroscopy" and "Saline infusion sonohysterography" and "Clinical manifestations and diagnosis of congenital anomalies of the uterus" and "Intrauterine adhesions".)
Diagnostic laparoscopy — The role of laparoscopy in the evaluation of infertility is controversial. Laparoscopy is invasive and expensive and does not usually alter the treatment of the infertile couple, particularly in couples in whom the HSG is normal. This is especially true if the clinician plans to recommend IVF relatively early in the couple's treatment plan, such as in cases of severe male factor or complete bilateral proximal tubal obstruction.
The advantages of performing laparoscopy in unexplained infertility are that it may reveal a specific cause of infertility and thus enable targeted therapy, including surgical therapy, while avoiding potentially ineffective or unnecessary empiric fertility treatments.
Generally, laparoscopy is indicated in women with otherwise unexplained infertility and a suspicion of endometriosis or pelvic adhesions due to a history of pelvic pain, complicated appendicitis, pelvic infection, pelvic surgery, or ectopic pregnancy [43-45]. Endometriosis, if identified, can be excised/ablated at the time of the diagnostic procedure.
One randomized controlled trial reported that laparoscopic ablation of minimal to mild endometriosis improved the fecundity of infertile women for at least nine months following the surgery [46]. A subsequent smaller randomized study of laparoscopic treatment of endometriosis could neither confirm nor refute this observation, possibly due to inadequate power [47].
There are currently no randomized trials assessing the cost effectiveness and timing of diagnostic laparoscopy prior to ovulation induction. As there is a relatively high likelihood (above 20 percent) of finding a significant abnormality at laparoscopy in a woman with normal testing [48,49], we suggest laparoscopic evaluation to couples with:
- Unexplained infertility, usually prior to initiating gonadotropin therapy
- Suspected endometriosis or pelvic adhesions due to a history of pelvic pain and/or previous surgery or infection.
When we perform laparoscopy, we also perform chromotubation to assess tubal patency and hysteroscopy to evaluate the uterine cavity. For this reason, if laparoscopy is planned, then HSG can be omitted [50].
The use of laparoscopy to treat infertility is covered in detail separately. (See "Laparoscopic surgery for treatment of infertility in women".)
TESTS OF LIMITED CLINICAL UTILITY
Postcoital test — We do not recommend postcoital testing [11]. The postcoital test is most frequently utilized to assess the adequacy of the cervical mucus and its interactions with sperm. After intercourse in the late follicular phase, the female partner is examined and a small amount of cervical mucus is obtained for assessment of spinnbarkeit (stretchability) and microscopic examination of ferning and sperm motility (at least 5 motile sperm per high power field is considered normal).
The postcoital test has been widely used in infertility investigations since 1866, but has limited diagnostic potential and poor predictive value [51,52]. There is no consensus on the normal range of sperm per high-power field and there is low inter- and intraobserver reproducibility [53]. The marked heterogeneity of results and the limitations of study design raise serious doubts about the utility of the postcoital test [54]. In addition, various treatments for abnormal test results have not been shown to be effective, and widely used infertility therapies (eg, intrauterine insemination, IVF) bypass the cervix. A randomized controlled trial comparing infertility investigations with and without the postcoital test showed no difference in pregnancy rates at 24 months [55]. Thus, incorporation of the postcoital test in standard infertility evaluations increases the number of tests and treatments but has no effect on the pregnancy rate.
Endometrial biopsy — Documentation of a secretory endometrium is a reliable indication of ovulation, but is invasive, expensive, uncomfortable, and unnecessary for ovulation evaluation.
Although endometrial receptivity during the implantation window is crucial for achieving pregnancy, no histological or biochemical assessment of endometrial responses has been reliably associated with conception [56-60]. This was illustrated in the following representative examples:
- A study of repeated endometrial biopsies in normal fertile women showed that 51 percent have a single out-of-phase biopsy (using two-day or greater lag criteria) and 27 percent have sequential out-of-phase biopsies [61].
- A study of 619 women with regular menstrual cycles compared the frequency of out-of-phase endometrium in fertile (n = 332) and infertile couples (n = 237) [62]. Daily LH testing was performed until an LH surge was detected and then the women were randomly assigned to endometrial biopsy on day 21-22 or day 26-27. An out-of-phase biopsy of greater than two days was actually more common in fertile women (49 versus 43 percent at D21-22, 35 versus 23 percent at D26-27).
Thus, it appears that luteal phase defect is often present in fertile women and histological dating does not discriminate fertile from infertile couples [61,62]. As the treatment of luteal phase defect does not improve pregnancy outcome in infertile women, luteal phase evaluation by histological dating of the endometrium is not worthwhile.
Basal body temperature records — Basal body temperature charts are the least expensive method for detecting ovulation, but interpretation of the charts can be difficult and subject to wide interobserver variation [63,64]. We prefer serum testing for assessment of ovulatory status. (See 'Assessment of ovulatory function' above.)
Progesterone released from the corpus luteum at the time of ovulation has potent effects on the hypothalamus, one of which is to increase body temperature. As a result, daily temperature monitoring can be used to document progesterone production and, therefore, ovulation. The woman takes her temperature by putting the thermometer under her tongue every morning while she is still in the basal state (ie, before she gets out of bed, uses the bathroom, or has anything to eat or drink) and records the temperature on a chart. Although there is an expected amount of daily variability, an approximately 0.5ºF rise in body temperature can be detected in the luteal phase of the menstrual cycle compared with the follicular phase. In a normal cycle, the temperature rise begins one or two days after the LH surge and persists for at least 10 days. Thus, temperature changes are sufficient to retrospectively identify ovulation, but they occur too late to be useful for timing intercourse.
Zona-free hamster oocyte penetration test — This test is also known as the sperm penetration assay. Conflicting literature exists on whether the hamster oocyte test predicts human oocyte fertilization [65,66]. The utility of test results depends, in part, on the experience of the laboratory performing the assay. We do not order this test since the results would not influence our clinical management. (See "Evaluation of male infertility", section on 'Zona-free hamster oocyte penetration test'.)
Mycoplasma cultures — We do not suggest obtaining routine Ureaplasma urealyticum and Mycoplasma hominis cultures given that there is minimal evidence for a role of these organisms in female infertility [67].
Testing for antibodies — Routine testing for antiphospholipid, antisperm, antinuclear, and antithyroid antibodies is not supported by existing data [68]. Although an association between antiphospholipid antibodies and recurrent pregnancy loss has been established, the other autoimmune factors remain under investigation as markers of fertility treatment failure. (See "Obstetrical manifestations of the antiphospholipid syndrome".)
Karyotype — There is a general consensus to karyotype the male partner if there is severe oligospermia, as these men are at high risk of microdeletion or other karyotypic abnormalities. We suggest karyotyping women with very early premature menopause (prior to age 40) and both partners if there have been recurrent pregnancy losses. In most other circumstances, karyotyping is not indicated as part of the initial evaluation because of the low incidence of abnormalities in women with unexplained infertility, endometriosis, or tubal factor infertility [69]. Karyotype may be useful in patients with these conditions who have failed initial treatment approaches and plan to undergo IVF, although the cost-effectiveness of universal karyotype screening prior to IVF has not been established [70].
SUMMARY AND RECOMMENDATIONS
- We suggest that an infertility evaluation be offered to couples who have not been able to conceive after 12 months of unprotected and frequent intercourse (Grade 2C). Earlier evaluation (eg, after six months) is indicated in some couples, such as those in whom the female partner's age is over 35 years or she has a history of oligo/amenorrhea, known or suspected tubal disease or endometriosis, a history of chemotherapy or radiation therapy, or a partner known to be subfertile. (See 'Timing' above.)
- The history and physical examination are directed at identifying signs and symptoms suggestive of the etiology of the infertility. (See 'History and physical examination' above.)
- The basic infertility evaluation of all couples consists of:
(1) - Semen analysis. (See 'Semen analysis' above.)
(2) - Assessment of ovulatory status by history or laboratory testing. (See 'Assessment of ovulatory function' above.)
(3) - Determination of tubal patency and presence or absence of abnormalities of the uterine cavity by hysterosalpingogram. (See 'Assessment of fallopian tube patency' above and 'Assessment of the uterine cavity' above.)
- We suggest assessment of ovarian reserve by day 3 FSH levels in women over 35 years of age and younger women with risk factors for premature ovarian failure. (See 'Assessment of ovarian reserve' above.)
- We suggest diagnostic laparoscopy for couples with unexplained infertility and women with suspected endometriosis or pelvic adhesions. (See 'Diagnostic laparoscopy' above.)
