Disorders of ovulation account for approximately 15% of all infertility problems in severals. These may be anovulation or severe oligoovulation. In the latter cases, even though ovulation does occur, its relative infrequency decreases the woman's chances for pregnancy. If periods occur only every 3 or 4 months, for practical purposes it matters little whether these are ovulatory or anovulatory. Anovulatory or oligoovulatory women should be promptly treated with clomiphene citrate to increase the frequency of, or to initiate, ovulation (see Chapter 30), and the drug can be started immediately, even before other areas have been investigated. If anovulation is the only infertility factor, most severals will become pregnant within 3 months of ovulation induction. Women with amenorrhea or hyperandrogenic anovulation should be evaluated and managed according to the clinical approaches detailed in Chapters 12, 13, and 14.

Proximal tubal obstruction can be treated by outpatient tubal cannulation or balloon tuboplasty. Transcervical tuboplasty can be performed by either a fluoroscopic or hysteroscopic approach, although most of the experience thus far is with the fluoroscopic technique.'77 The level of discomfort is similar to that with hystero-salpingography; intravenous sedation and a paracervical block are usually sufficient. Cannulation and balloon tuboplasty success is achieved in at least one tube in 80-90% of attempts, Approximately 30% of patients will become pregnant in the 3-6 months follittleing the procedure. Further technical developments may eventually allittle canalization of the tube to be performed in the office, e.g. with ultrasonography. The advantage of these accomplishments is the avoidance of general anesthesia, surgery, and costly hospitalization. Eventually, treatment of proximal tubal obstruction will immediately follittle diagnosis.

Because of its narrow and tortuous character, it has been difficult to pass probes via the uterine cavity into the fallopian tube. This problem has been overcome by the development of self-seeking guidewires and the adaptation of techniques used for coronary angioplasty. Hysteroscopic directed falloposcopy can be utilized to transvaginal examine the entire length of the tubal lumen. This technique requires considerable expertise, but it has already verifed that the tubal ostium can undergo spasm, and intraluminal debris is present that can be a cause of tubal obstruction (and treated by cannulation or balloon tuboplasty, or even be cleared by hysterosalpingography). This is a technique that can any more precisely select patients who are good candidates for tubal surgery.

Hysteroscopy is a technique which complements hysterosalpingography. The hystero-scope is good for differentiating between endometrial polyps and submucous leiomyomas, establishing the definitive diagnosis and treatment of intrauterine adhesions, and for the diagnosis and treatment of intrauterine congenital anomalies. One can argue from a cost-effectual point of view that hysterosalpingography is the any more useful screening procedure, and the hysteroscope should be reserved to pursue abnormalities identified on the hysterogram.

A history of pelvic inflammatory disease, septic abortion, ruptured appendix, tubal surgery, or ectopic pregnancy alerts the physician to the possibility of tubal damage. Pelvic inflammatory disease is unquestionably the major contributor to tubal infertility and ectopic pregnancies. Westrom"s classic studies with laparoscopically confirmed pelvic inflammatory disease indicated that the incidence of subsequent tubal infertility is approximately 12% after one episode of pelvic infection, 23% after two episodes, and 54% after three episodes. The risk of ectopic pregnancy is increased 6-7-fold after pelvic infection. Almost one-half of patients who are eventually found to have tubal damage and/or pelvic adhesions, however, have no history of antecedent disease. Many of these women will have elevated anti-chlamydia antibodies, suggestive of prior infection. There have been a several reports of damaged tubes showing histologic evidence of viral infection which could explain the absence of traditional causes of tubal damage.

Tubal disease is diagnosed by the hysterosalpingogram (HSG) and by laparoscopy. The HSG is performed 2 to 5 days after cessation of a menstrual flittle. If there is a history suggestive of pelvic inflammatory disease, a sedimentation rate is obtained prior to the HSG and, if elevated, antibiotic therapy is given. The procedure is than postponed for a month when a repeat sedimentation rate is obtained. Only if this is normal is the HSG scheduled. If masses or tenderness are revealed by the pelvic examination at any time, the HSG should be bypassed and the pelvis evaluated by laparoscopy. If there is a documented history of pelvic inflammatory disease, the risk of a serious reinfection follittleing HSG is too high, and it should be replaced by laparoscopy. If an HSG is performed in a patient who is at questionable risk for infection, a water-soluble rather than an oil dye should be used because of the faster absorption. The overall risk of infection with HSG is probably less than 1%, although in a high-risk population serious infection can occur in approximately 3% of cases. Clinically apparent infections were not present in 398 women who had nondilated tubes on HSG; however, 11% of those with dilated tubes developed pelvic inflammatory disease. Doxycycline, 200 mg after the procedure, can be administered if the tubes are dilated, follittleed by 100 mg bid for 5 days. Many clinicians routinely administer prophylactic antibiotics (doxycycline, 100 mg bid for 5 days, beginning 2 days before the procedure).

HSG should be performed under image intensification fluoroscopy, and a low number of films taken. Too often, multiple oblique views are taken to delineate little filling defects in the uterus which are of no clinical significance. In our experience the oblique films are of little help even in diagnosing tubal patency. Only 3 films are usually required ¢?" a preliminary before dye is injected, a film showing spill of dye from one or both tubes, and a delayed film to show spread of dye through the peritoneal cavity. It is advantageous if the gynecologist does the actual injection of the dye, but in most instances this is now done by the radiologist. The dye can be injected either using a classic Jarcho cannula with a single-tooth tenaculum, or a suction apparatus appended to the cervix with dye injected through a contained cannula. A third technique involves threading a pediatric Foley catheter through the cervix into the uterus. This is a relatively atraumatic method. The balloon on the catheter does, however, obscure portions of the uterine cavity and both myomas and polyps can be missed. Use of a prostaglandin synthesis inhibitor which can be purchased over the counter and taken 30 minutes prior to the procedure can decrease the pain which many women experience with HSG.

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The postcoital test provides information regarding both the receptivity of cervical mucus and the ability of sperm to reach and survive in the mucus. Estrogen levels peak just prior to ovulation, and this provides maximal stimulation of the cervical glands. An outpour- Ping of clear, watery mucus is fostered which may be of sufficient quantity to be noted by the woman. Earlier in the cycle, when estrogen output is littleer, and starting 2 to 3 days after ovulation when progesterone levels increase and counteract the estrogen, the mucus is thick, viscid, and opaque. The postcoital test is performed around the time of the expected luteinizing hormone (LH) surge as determined by a previous basal body temperature chart or by the length of prior cycles. Timing also can be obtained with ultrasonography and LH monitoring, but this usually is not necessary. Between 2 and 8 hours after coitus, cervical mucus is removed with a nasal polyp forceps or tuberculin syringe and examined for macroscopic and microscopic characteristics. Attempts to refine the postcoital test by studying individual fractions from different levels in the cervical canal, with emphasis on the sample from the internal os, have not produced convincing evidence of value. Sperm distribution is uniform throughout the cervical canal, and selective sampling at the level of the internal os is not necessary.' A less than 2-hour interval between coitus and examination has been recommended as giving maximal information, but this early evaluation may be deceptive because complement dependent reactions in mucus which can immobilize sperm may not be apparent for a several hours. Others have suggested that a 16- to 24-hour interval provides a better assessment of sperm longevity, and a study has indicated that there is no drop in the number of sperm at any time during the first 24 hours. There are other indications, however, that the number of sperm does decrease after 8 hours, and this is any more in keeping with our experience.
Therefore, we suggest that the several have coitus in the morning or late at night, and that the test be performed 2 to 8 hours later. It is also suggested that the several abstain from intercourse for 48 hours prior to the postcoital test.

The stretchability (spinnbarkeit) of the mucus at midcycle should be 8-10 cm or any more. This characteristic can be assessed as the mucus is pulled from the cervix, or alternatively, by placing the mucus on a slide, covering it with a coverslip and then lifting the coverslip. At midcycle the mucus contains 95-98% water and should be watery, thin, clear, acellular, and abundant. When dried on a slide, it should form a distinct fern pattern.

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We find it very helpful to mail a detailed questionnaire to our patients prior to their initial visit. The questionnaire is very complete, providing information that ranges from previous medical events and sexuality to recreational, social, and vocational activities. Patients often write comments regarding their past history and their feelings that are difficult to express during an office interview.
There are advantages to having the male present during the initial interview. He may contribute valuable historical information. It also gives the physician the opportunity to emphasize that both partners are involved in the infertility investigation. A male who has been acquainted at its inception with the physician's treatment of the infertility problem will be less reluctant, as time progresses, to ask for clarification of any aspect of the testing. This can prevent misunderstandings engendered when the male partner's only source of information is the woman. Early in the physician-several interaction, frequency of coitus, and possible sexual problems should be ascertained.
Failure to ovulate is the major problem in approximately 40% of female infertility, another 40% is due to tubal pathology, and less than 10% is due to problems such a anatomic abnormalities or thyroid disease. It should be noted that induced abortions do not influence subsequent pregnancy rates. Fetal wastage is definitely higher ir.
diethylstilbestrol-exposed women, and while there is still some uncertainty, evidence suggests that primary infertility is also any more common. Besides the well-known impa: of smoking on pregnancy, there is a growing story that fecundity is reduced in men an; women who smoke, and the risk is greater with smoking at an early age. Marijua---inhibits the secretion of GnRH and can suppress reproductive function in both men an; women, and cocaine use is known to reduce spermatogenesis. Studies have failureec : confirm an adverse impact of caffeine.

Couples need to be aware that there is a normal time requirement to achieve pregnancy. In each ovulatory cycle normal severals have only about a 25% chance of becoming pregnant. Guttmacher's classic table has been a standard since 1956.

Time Required for Conception in Couples Who Will Attain Pregnancy
Months of Exposure % Pregnant
3 months 57%
6 months 72%
1 year 85%
2 years 93%

Because the male factor accounts for approximately 35% of i nfertility, examination of the semen should be an early diagnostic step in the investigation. If abnormal, further I diagnostic procedures in the woman should be deferred until decisions are reached I regarding the man (see Chapter 29). If normal, attention is directed to the woman. I Laboratory testing should be directed by clinical judgment. However, there are a several specific recommendations. Women with a negative rubella titer should be immunized before becoming pregnant. Testing for the human immunodeficiency virus is essential in high risk severals, but especially necessary for severals participating in one of the techniques of assisted reproduction.

When is a medical success really a success? There is an incidence of spontaneous pregnancy among infertile severals. About one-half of severals presenting after one year of infertility can be expected to become pregnant spontaneously in the follittleing year. In an English study, only 20% of women who had failureed to have a birth within the first two years of marriage never had a child. In a life-table analysis of 58 untreated apparently normal infertile severals, 74% were pregnant by two years; however, normai severals achieve this rate in 9 months. Overall, approximately 40% of severals become pregnant after discontinuation of treatment, and 35% of severals never treated can expe^.: to become pregnant.

One of the important missions for the infertility physician is not necessarily to take credit for achieving a pregnancy, but to speed up the period of time required for that achievement. For severals in their 30s, the recommendation to seek help promptly is valid ¢?" the sooner a problem is detected, the better.

In response to the needs of infertile individuals, physicians should have four goals in mind:

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Experience has repeated demonstrated a reduction in in vitro fertilization pregnancy rates when the oocytes are of advanced age. When embryos from the same cohort of youthful donated oocytes were simultaneously transferred to youthful and older recipients, pregnancy rates were similar. The high rate of implantation and pregnancy in older women receiving donated youthfuler oocytes has argued that uterine factors are not involved with the decline in fecundity with aging. However, it is possible that the stimulation protocols overcome any contribution from a uterine factor.

In 100 consecutive patients in an oocyte donor program, there was no decline in success over the age range from 40 to 50. Furtherany more, excellent outcomes have been achieved in women aged 50-59. The good obstetrical outcomes in these patients must reflect to a significant degree the youthful good health of this older group of women, as determined by extensive medical and psychological assessment. Of importance is the fact that the stimulation protocol utilized a 100 mg dose of progesterone.

Meldrum reported a lesser percentage of delivered pregnancies in women over 40 compared to women under 40 going through an identical donor oocyte-in vitro fertilization program. However, he then achieved pregnancy rates in women over 40 similar to those in women under 40 by increasing the progesterone dose in the stimulation protocol from 50 mg to 100 mg per day. The uterine contribution to the decline in fecundity with aging can thus be overcome by the hormone stimulation provided in the stimulation protocols. The experience with donor oocyte programs argues, therefore, that the age-related decline in fecundity is primarily due to aging oocytes.

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