Infertility

Essentials of Diagnosis ++Both male and female evaluation are needed to reach diagnosis.Male partner: HistorySemen analysisIf semen analysis abnormal, referral to urology, endocrine evaluation, and karyotyping in severe casesState-mandated infectious disease panel if treatment includes intrauterine insemination or in vitro fertilizationFemale partner:History, confirm ovulationPhysical exam to assess cervix, uterus, and adnexa for pathologyCycle day 3 blood work and ultrasound to assess ovarian reserveHysterosalpingogram to evaluate uterine cavity and fallopian tubesPossible saline sonogram to evaluate uterine cavityLaparoscopy to assess endometriosis when indicatedState-mandated infectious disease panel if undergoing in vitro fertilization+ Infertility: Introduction ++The number of infertility visits has increased over the past decades. In some cases, couples have voluntarily delayed childbearing in favor of establishing careers and may experience an age-related decline in fertility. There have been significant advances in assisted reproductive technologies (ART), from improved embryo culture media to intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD), which have resulted in remarkable increases in in vitro fertilizationembryo transfer (IVF-ET) pregnancy rates. These advances coupled with increasing public awareness and acceptance of ART have spurred women or couples with infertility to seek medical care.++Definition++Infertility is defined as the inability of a couple to conceive within 1 year. Sterility implies an intrinsic inability to achieve pregnancy, whereas infertility implies a decrease in the ability to conceive and is synonymous with subfertility. Primary infertility applies to those who have never conceived, whereas secondary infertility designates those who have conceived at some time in the past.++Fecundity is the probability of achieving a live birth in 1 menstrual cycle. Fecundability is expressed as the likelihood of conception per month of exposure. Fertility, as well as infertility, of a woman or couple is best perceived as fecundability, as few infertile patients are sterile. It also allows for a direct comparison of treatment options over a more functional time frame.++The prevalence of women diagnosed with infertility is approximately 13%, with a range from 7 to 28%, depending on the age of the woman. It has remained stable over the past 40 years; ethnicity or race appears to have little effect on prevalence. However, the incidence of primary infertility has increased, with a concurrent decrease in secondary infertility, most likely as a result of social changes such as delayed childbearing.++In normal fertile couples having frequent intercourse, the fecundability is estimated to be approximately 2025%. Approximately 8590% of couples with unprotected intercourse will conceive within 1 year. Sterility affects 12% of couples.+ Pathogenesis ++Infertility can be due to either partner or both. Overall, an etiology for infertility can be found in 80% of cases with an even distribution of male and female factors, including couples with multiple factors. A primary diagnosis of male factor is made in approximately 25% of cases. Ovulatory dysfunction and tubal/peritoneal factors comprise the majority of female factor infertility. In 1520% of infertile couples, the etiology cannot be found, and a diagnosis of unexplained infertility is made.+ Prevention ++Prevention of infertility is difficult to achieve and thus discuss, as a couple isn't really aware of the diagnosis until they try to achieve pregnancy. Although difficult to do, there are a few steps one can take to possibly decrease risk of infertility.++Although infertility is defined as the failure to achieve pregnancy after 12 months or more, earlier evaluation may be justified depending on one's history and is warranted for women over the age of 35. Because fertility is related to aging in women and perhaps in men after the age of 50, one should be aware of these risks when considering delaying childbearing. Therefore, it is the responsibility of the primary care provider or gynecologist to openly discuss fertility and aging during a well-woman visit. The new techniques of oocyte cryopreservations hold a great promise for women who would like to delay childbearing and should be addressed with women to increase awareness.++Weight extremes have also been associated with infertility in women, mainly due to anovulation. Thus a healthy lifestyle may improve fertility for women with ovulatory dysfunction. However, beyond what has been mentioned previously, there is little evidence that dietary variations enhance fertility. Women should also be advised to take folic acid supplement (at least 400 g daily) when trying to conceive.++Smoking has a substantial adverse effect on female fertility demonstrated by a recent meta-analysis and also causes abnormalities in male semen parameters. Thus couples who smoke and are trying to conceive should be advised accordingly. Moderate alcohol and caffeine consumption has no adverse effect on fertility; however. higher levels of alcohol and recreational drugs should be discouraged for couples trying to conceive.++Lastly, couples trying to conceive should be advised to avoid using vaginal lubricants as these can be toxic to sperm based on their effect demonstrated in vitro. If needed, it may be better to recommend mineral oil, canola oil, or hydroxyethylcellulose-based lubricants.Differential Diagnosis & Clinical Findings ++The armamentarium of diagnostic tests available for the evaluation of an infertile couple is large. Therefore, a clinician should be judicious in his/her use of tests. The history and physical exam shape the endocrinologic and radiologic testing algorithm specific to each patient. Other factors to consider include patient age, risks associated with the test, invasiveness, expense, and probabilities of significant findings (Table 531). The patient(s) should be included in the decision-making process.++Table Graphic Jump Location

Table 531. Causes of Infertility.View Large|Save TableTable 531. Causes of Infertility.Male FactorOvulatory Factor (cont.)

Endocrine disordersPeripheral defects

Hypothalamic dysfunction (Kallmann's syndrome)Gonadal dysgenesis

Pituitary failure (tumor, radiation, surgery)Premature ovarian failure

Hyperprolactinemia (drug, tumor)Ovarian tumor

Exogenous androgensOvarian resistance

Thyroid disordersMetabolic disease

Adrenal hyperplasiaThyroid disease

Anatomic disordersLiver disease

Congenital absence of vas deferensRenal disease

Obstruction of vas deferensObesity

Congenital abnormalities of ejaculatory systemAndrogen excess, adrenal or neoplastic

Abnormal spermatogenesisPelvic Factor

Chromosomal abnormalitiesInfection

Mumps orchitisAppendicitis

CryptorchidismPelvic inflammatory disease

Chemical or radiation exposureUterine adhesions (Asherman's syndrome)

Abnormal motilityEndometriosis

Absent cilia (Kartagener's syndrome)Structural abnormalities

VaricoceleDiethylstilbestrol (DES) exposure

Antibody formationFailure of normal fusion of the reproductive tract

Sexual dysfunctionMyoma

Retrograde ejaculationCervical Factor

ImpotenceCongenital

Decreased libidoDES exposure

Ovulatory FactorMllerian duct abnormality

Central defectsAcquired

Chronic hyperandrogenemic anovulationSurgical treatment

Hyperprolactinemia (drug, tumor, empty selia)Infection

Hypothalamic insufficiency

Pituitary insufficiency (trauma, tumor, congenital)

++New Patient Assessment++The initial aspect of the interview includes discussion of the factors (ie, ovulation, sperm concentration, ovarian reserve, etc.) that affect fertility so that the patient(s) is aware of the potential etiologies. In this light, the physician can present an algorithm for the diagnostic evaluation that the patient will understand. This will help the patient grasp the peculiarities of the specific tests, such as timing the hysterosalpingogram to the day of the menstrual cycle, and provide an opportunity for the patient(s) to ask fertility-related questions and to address any information learned from friends, family, or the Internet.++The initial clinical assessment should begin with a thorough history of both partners. Factors to consider while obtaining the medical history are outlined in Table 532 for the female and in Table 533 for the male. The history should guide the physical examination beyond the general evaluation; for example, a rectovaginal exam to detect uterosacral ligament nodularity associated with endometriosis is indicated if a woman presents with a history of severe dysmenorrhea. However, a thorough physical exam may divulge key information such as acanthosis nigricans and its association with insulin resistance.++Table Graphic Jump Location

Table 532. Medical History for Female Factor Infertility.View Large|Save TableTable 532. Medical History for Female Factor Infertility.In utero diethylstilbestrol (DES) exposure

History of pubertal development

Present menstrual cycle characteristics (length, duration, molimina)

Contraceptive history

Prior pregnancies, outcomes

Previous surgeries, especially pelvic

Prior infection

History of abnormal Papanicolaou (Pap) smear, treatment

Drugs and medications

General health (diet, weight stability, exercise patterns, review of systems)

++Table Graphic Jump Location

Table 533. Medical History for Male Factor Infertility.View Large|Save TableTable 533. Medical History for Male Factor Infertility.Congenital abnormalities

Undescended testes

Prior paternity

Frequency of intercourse

Exposure to toxins

Previous surgery

Previous infections, treatment

Drugs and medications

General health (diet, exercise, review of systems)

Decreased frequency of shaving

++The laboratory and radiologic tests assess 4 key aspects for fertility in a couple: the sperm (male factor), the oocyte (ovulatory factor and ovarian reserve), transport (pelvic factor including fallopian tubes), and implantation of ova (uterus). In many cases, the couple will be attempting to absorb significant amounts of information, some of which may be highly technical, at a time of heightened emotion. It is therefore helpful to offer literature or a written summary of the discussion. Frequently, the initial history will indicate a probable diagnosis or a contributing cause of infertility, but it is important to complete a basic evaluation of all of the major factors so a secondary diagnosis is not ignored.++Evaluation of Male Partner++Male factor is diagnosed in 2540% of infertile couples. The majority of the diagnoses involve testicular pathology such as varicocele. Although validation is incomplete, there is a trend toward increasing use of molecular techniques to quantify the fertility potential of semen as our knowledge of fundamental molecular genetics expands. Experience and investigation have relegated several tests previously used to assess fertilization to historical interest. Beyond the history and physical exam, the initial evaluation of male factor is through semen analysis. If abnormal, the semen analysis should be repeated in 4 weeks or more to confirm findings. Normal semen analysis excludes any important male factor, whereas abnormal semen analysis suggests the need for further evaluation (endocrine, urological, or genetic).++Semen Analysis++The male partner should abstain from coitus for 25 days before collecting the sample, and the specimen should be received in the lab within 1 hour of collection. Table 534 lists normal sperm values. If fundamental parameters of count and motility are normal, the assessment of the morphology of the sperm becomes more critical. Specialized expertise in determining sperm morphology and strict application of criteria should be used before declaring the semen normal.++Table Graphic Jump Location

Table 534. Normal Semen Parameters.View Large|Save TableTable 534. Normal Semen Parameters.Liquefaction30 minutes

Count20 million/mL or more

Motility>50%

Volume2 mL or more

Morphology

WHO criteria>30% normal

Kruger Strict Criteria>14% normal

pH7.27.8

White blood cell count