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New Treatments for Infertility

Infertility is defined as the failure of a couple to es­tablish a pregnancy after 1 year of coitus without using contraception. The expected monthly conception rates among healthy young couples is about 20-25%. Female fertility decreases significantly after age 35. Approximately 15% of couples are infertile; in 15 % of these couples, no etiology can be identified by usual clinical and laboratory techniques. Using a "normal" cumulative fecundability curve, 95% of couples attempting pregnancy should conceive within 13 months. Fecundity refers to the potential for a couple to reproduce.

    The rate of infertility has appeared to increase in the United States over the past 25 years in response to several factors: an increase in sexually transmissible infections (in part associated with the increased use of nonbarrier methods of contraception), deferral of age for childbearing, societal changes in which infertility is discussed more openly, and widespread publicity of new methods for achieving fertility among infertile couples. The evaluation of a couple that has been unable to conceive can be under­taken before a 12-month trial if a woman is anovulatory, if one of the partners has had a sterilization procedure, or if a woman is 35 years of age or older.

    Establishment of pregnancy depends on the presence of several key factors:

       Release of an ovum from the ovary (ovulation), preferably on a regular cyclic basis 

  Production of an ejaculate containing an ample number of morphologically normal, motile spermatozoa

 •  Deposition of spermatozoa in the female reproduc­tive tract at or near the cervical os

 •     Survival of spermatozoa within the female repro­ductive tract

 •     Arrival of the ovulated ovum in the fallopian tube

 •     Patency and normal physiologic function of the fallopian tube

 •     A normal intrauterine environment that enables migration of spermatozoa from cervix to tubal ostia and fosters embryonic implantation

 •     Fusion of gametes within the tubal lumen

 •     Transfer of the embryo into the uterine cavity

     Evaluation of an infertile couple requires a detailed medical, sexual, and reproductive history. Specific ele­ments to evaluate include length of time the couple has attempted to conceive, prior reproductive performance of each partner, menstrual cyclicity, symptoms suggestive of pelvic inflammatory disease or endometriosis, coital tech­nique (timing, frequency, and level of satisfaction), use of medications, previous abdominal or pelvic surgery of the female, and urologic disorders of the male. Women should be given a thorough physical and pelvic examination, in­cluding an assessment of cervical cytology and cervical cultures (Chlamydia, gonorrhea, Ureaplasma). Preconceptional evaluation should accompany the history, and coun­seling and appropriate studies should be a part of the management plan.

    A thorough initial evaluation involves analysis of se­men, cervical and coital factors (a postcoital test), ovulation (basal body temperature, late-luteal-phase endometrial biopsy or a luteal-phase serum progesterone determina­tion or both, and home ovulation detection kit), uterine and tubal factors (hysterosalpingography, possibly hysteroscopy), and peritoneal factors (laparoscopy with tubal chromotubation). Abnormalities found in any of these studies require a more detailed investigation. The basic appraisal should identify targets for correction in approxi­mately 85% of couples. When causes of infertility are ana­lyzed, they can generally be attributed to the male in 40-50% of couples, to tubal and peritoneal factors in 25­30%, to ovulatory defects in 20-25%, and to cervical and uterine factors in 10%. Frequently, more than one factor contributes to a couple's infertility. The basic evaluation of an infertile couple can be expeditiously completed in 2-3 months. When the evaluation is complete, the couple must be provided with detailed options and statistics for outcome associated with each approach to correction.

INVESTIGATION AND TREATMENT OF THE INFERTILE MALE

Male infertility is the cause of approximately 40% of all couples' inability to conceive. Thus, the obstetrician-gynecologist should be familiar with the available diagnos­tic and treatment approaches to the infertile male. 

History and Physical Examination

The history and physical examination are used to discover evidence of possible pre-testicular, testicular, or post-testicular disorders that may result in male infertility by one of several mechanisms: 1) abnormalities of sperm production, 2) disordered maturation within the male reproduc­tive tract, 3) abnormal sperm function.

Laboratory Tests

The evaluation of the potentially infertile male initially involves screening with semen analyses, followed by fur­ther examination when warranted. However, normal se­men results do not exclude male causes of the couple's infertility. If the complete evaluation of the female partner fails to establish a cause for the couple's infertility, further subsequent examination of the male partner with special­ized testing of sperm function is indicated. Virtually all semen samples, no matter how abnormal, could be candi­dates for assisted fertilization.

Evaluation of Sperm Function

Additional studies may be selectively used to further evalu­ate sperm transport in the female reproductive tract, sperm capacitation and acrosome reaction, zona pellucida bind­ing, sperm-egg fusion and penetration, and sperm decondensation within the oocyte cytoplasm. Sperm transport is initially assessed by the postcoital test, with addi­tional in vitro tests of sperm-mucus interaction to further characterize the abnormality detected on the postcoital test. Sperm-mucus interaction can be assessed by examination of sperm penetration through a mucus interface under the microscope and crossed-hostility tests with donor mucus.

Treatment

Despite significant recent advances in the treatment of fe­male infertility, successful specific medical and surgical treatment can be offered in no more than 10% of male infertility cases. The treatment of any infertile male ulti­mately depends both on an accurate determination of the underlying pathophysiologic process leading to disordered sperm production, delivery, or function and a thorough evaluation of the female partner. Those conditions for which specific therapy with proven efficacy are available include surgical repair of varicocele and some cases of obstructive azoospermia.