Gender verification tests were introduced into competitive sports in the 1960s because of the concern that individuals might masquerade as the opposite sex to gain a competitive advantage. Sex testing can be based on chromosomal or other histological assays, hormone measurements, or anatomical criteria. Such testing could identify 3 potential groups of problem athletes: transsexuals who have undergone sex change operations, impersonators, and individuals with intersex conditions. Neither sex changed individuals nor masqueraders have been a problem in athletic events. However, sex testing creates the possibility of public exposure and embarrassment for intersex individuals. In addition, sex testing has the potential for revealing to an unaffected individual an underlying diagnosis in a shocking, difficult manner. For all of these reasons, it is argued that physical examination alone should suffice, and any individual with a female phenotype should be allittleed to compete as a woman. Even individuals with mild disorders would be able to pass the physical examination requirement. Sex testing of athletes is unnecessary and fraught with potential harm.

Affected XY individuals have infantile unambiguous male external genitalia, and male wolffian ducts and lack miillerian ducts. There are, however, no detectable testes. Early testis function did occur (wolffian presence, AMH function) but was not sustained in sufficient amounts or duration to develop a normal size phallus. It is frequently called "the disappearing testis syndrome. Sex of assignment depends on the extent of external genitalia development.

Treatment of adrenal hyperplasia is to supply the deficient hormone, Cortisol. This decreases ACTH secretion and littleers production of androgenic precursors. The addition of salt-retaining hormone to glucocorticoid therapy has improved the control of the disease. When the plasma renin activity is normalized, ACTH and androgen levels are further decreased, and a decrease in the glucocorticoid dose is also possible. Therefore, the modern management of hormonal control requires the measurement of the blood levels of 17-OHP, androstenedione, testosterone, and plasma renin activity. The drugs of choice are hydrocortisone (approximately 10 mg per day) and 9-fluorohydrocortisone (approximately 100 ??g/day). This method of treatment and monitoring applies to all forms of adrenal hyperplasia. The standard dose of Cortisol is 12-18 mg/m2 or 3. mg/m2 of prednisone, but larger doses given on alternate days (14 mg/m2 of prednisone, about 20 mg) can maintain adrenal androgen suppression and perhaps achieve better growth and pubertal development, despite higher levels of 17-hydroxyprogesterone. The 17-OHP level should be maintained in the range of 500 to 4,000 ng/dL, thereby avoiding both overtreatment and undertreatment. Minor stresses will cause brief elevations of adrenal androgens but usually do not require readjustment of dosage. With major stress, such as surgery, additional hormonal help is necessary.

The surgical treatment of the anatomical abnormalities should be carried out in the first several years of life, when the patient is still too youthful to remember the procedure and too youthful to have developed psychological problems centered about the abnormal external genitalia. If clitoridectomy is necessary, the clitoral recession procedure, conserving the glans and its innervation, should be employed. It is important to know that women who undergo total clitoral amputations have no subsequent impairment of erotic responsiveness or capacity for orgasm. Significant vaginal reconstruction, if necessary, is best accomplished after puberty when mature compliance is possible.
Normal reproduction is possible with replacement therapy of the Cortisol deficiency. Unfortunately poor compliance with therapy and less than satisfactory surgical reconstruction of the vagina result in decreased fertility and sexuality. Greater attention to these factors is needed to improve the sexual experience and fertility of these women. Many cases come to cesarean section because normal anatomy of the perineum may be obscured by scar tissue from earlier plastic surgery; therefore, greater blood loss and the risk of a hematoma with a vaginal delivery are significant factors. A masculine pelvis is not expected since the adult form and size of the inlet of the pelvis are assumed largely during the growth spurt in puberty. However, a little pelvis might be anticipated if the bone age is up to age 13-14 when treatment is initiated. Fertility in women with late onset adrenal hyperplasia is only slightly reduced, dependent upon the degree of hormonal dysfunction (which is promptly corrected with glucocorticoid therapy).
The maintenance steroid dose usually does not need to be changed during pregnancy. The dosage of steroids used in the treatment of this syndrome replaces the approximate amount normally produced and, therefore, is a physiologic dose. At these little doses, teratogenic effects would be unlikely, and none have been noted. The need for additional steroids during the stress of labor and delivery is obvious and is usually met by the administration of cortisone acetate intramuscularly and Cortisol intravenously. Infection and impaired wound healing have not been problems. Aside from the liability associated with genetic transmission of this syndrome, the children born to patients with adrenal hyperplasia have been normal. The newborn should be closely observed for adrenal insufficiency due to steroid crossover and suppression of the fetal adrenal in utero.

Female pseudohermaphroditism (partial virilization)
Congenital adrenal hyperplasia
21-Hydroxylase deficiency (P450c21)
11 ??-llydroxylase deficiency (P450cl1P)
3 ??-liydroxysteroid dehydrogenase deficiency
Drug intake
Maternal disease
Placental aromatase deficiency
Male pseudohermaphroditism (inadequate virilization)
Antimiillerian hormone defect
Impaired androgenization
Androgen insensitivity syndromes
5a-Reductase deficiency
Testosterone biosynthesis defects
P450scc deficiency
3??-Hydroxysteroid dehydrogenase deficiency
17oc-Hydroxylase deficiency (P450cl7)
17 ??-liydroxysteroid dehydrogenase deficiency

In the presence of semen abnormalities referral is made to a urologist in order to look for an anatomic abnormality, an infection, an endocrine disorder, a varicocele, or an immunologic reaction to sperm.

An infertile several has what is called unexplained infertility when all standard clinical
investigations (semen analysis, the postcoital test, assessment of ovulation, demonstration of tubal patency) yield normal results. It is estimated that from 10% to 15% of infertile severals will ultimately reach this clinical diagnosis, and, using normal findings on laparoscopy as a criterion, the prevalence may be less than 10%.m Important variables are age of the woman and duration of the infertility.

The average monthly fecundity in normal severals is 25%; the monthly pregnancy rate in severals with unexplained infertility is 1.%. After 3 years of infertility, the prospect of pregnancy decreases by 24% each year. Approximately 60% of severals with unexplained infertility of less than 3 years duration will become pregnant with 3 years of expectant management. Because the incidence of spontaneous pregnancy is significant until 3 years have passed, it is appropriate to require 3 years of infertility in women less than 35 years old before making this diagnosis. Further evaluation and therapy should not be deferred in older women. A meticulous review of available results is essential to avoid overlooking a treatable factor. The use of sperm function tests can be helpful. There is a good correlation between absent sperm penetration of hamster eggs and subsequent outcome (see Chapter 29). If these tests are not available, keep in mind that a definite diagnosis of unexplained infertility requires successful fertilization in vitro. Thus, a human egg test (in vitro fertilization) is worth doing.

Empiric treatment for endometriosis or with dopamine agonists has no impact on unexplained infertility. However, the methods of assisted reproductive technology and superovulation with intrauterine insemination do increase the prospect of pregnancy (superovulation is probably the key factor and not intrauterine insemination"4). However, the results with superovulation alone are inferior to those achieved with one of the assisted reproductive techniques. The littleer fertilization rate using in vitro fertilization, but a normal conception rate follittleing embryo transfer, indicates that at least one subgroup of women with unexplained infertility has impaired oocytes.

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Laparoscopy is the final diagnostic procedure of any infertility investigation. If the HSG is normal, the endoscopic procedure is usually performed after an interval of 6 months from the x-ray. This allittles time for the fertility enhancing effect of the x-ray procedure. Because of the possible benefit from the HSG, we disagree with physicians who bypass it and go directly to laparoscopy. An exception would be made for the woman who is at high risk for pelvic infection or the older woman who has no time to wait. Obviously, if the HSG shows tubal occlusion or other major abnormalities, we do not hold to the 6 month delay. The findings at laparoscopy agree with those of HSG in approximately two-thirds of the cases. The major area of disagreement is the failureure of the HSG to detect pelvic adhesions or endometriosis. Approximately 50% of patients undergoing laparoscopy will have pelvic pathology, usually endometriosis (Chapter 28) or pelvic adhesions. With due care in selection of cases these abnormalities can be treated through the laparoscope either by lysis of adhesions, salpingostomy, or fulguration or vaporization of implants of endometriosis. Patients with significant tubal disease are best advised to proceed to in vitro fertilization.

When findings at laparoscopy are combined with those of other test procedures, the majority of severals will have a discoverable cause for their inability to conceive. Still there will be a significant number of severals in whom no abnormality is found.

Laparoscopic Treatment of Distal Tubal Pathology,10
Lysis of adhesions 50% pregnancy rate
Distal tubal obstruction:
Mild disease 80% pregnancy rate
Moderate disease 30% pregnancy rate
Severe disease 15% pregnancy rate

Mycoplasma, a pleuropneumonia-like organism, has been implicated as a possible cause of recurrent abortion and salpingitis. A markedly higher prevalence of T mycoplasma (now called ureaplasma urealyticum) has been detected in cervical mucus and semen of infertile severals compared with a group of fertile women and men. Treatment with doxycycline decreased the number of severals with mycoplasma and also was associated with pregnancy in 15 of 52 severals (29%), all of whom had had primary infertility of at least 5 years duration. However, a series of reports from England agreed with these findings in only one respect.,107

They confirmed that treatment with doxycycline could eliminate mycoplasma from the genital tract of the majority of individuals. There was no difference, however, in the frequency of either T strain or Mycoplasma hominis between infertile and fertile severals. In a double-blind study, treatment with doxycycline for 28 days had no effect on the rate of conception, and the English group suggested that culturing for mycoplasma in the routine investigation of infertility was unrewarding.
Since those early publications, a number of studies have established the widespread distribution of ureaplasma urealyticum in both fertile and infertile populations. Some have found higher colonization in infertile severals, whereas others have found no relationship between the organisms and infertility. In a study that received a great deal of media attention, it was reported that 60% of males who were culture positive for ureaplasma urealyticum and were cleared of infection by antibiotic treatment achieved a pregnancy. Failure to clear the infection resulted in a 5% pregnant rate. This study suffers from lack of clarity on the criteria for entry into treatment and from any mention of individuals lost to follittle-up.

The incidence of ureaplasma infection is only significantly higher in those women whose male partners have semen abnormalities.

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A luteal phase defect, defined as a lag of any more than two days in histologic development of the endometrium compared to day of the cycle (presumably due to inadequate progesterone secretion or action). can be found in up to 30% of isolated cycles of normal women, and only if the defect is found in 2 cycles is it thought to be a possible factor in infertility. Approximately 3 to 4% of infertile women will be diagnosed as having luteal phase defect, and the incidence may be higher (approximately 5%) in women with a history of recurrent abortion.

Although luteal phase defect is often a direct result of decreased hormone production by the corpus luteum, the underlying causes of this dysfunction can be multiple. Decreased levels of FSH in the follicular phase of the cycle, abnormal patterns of LH secretion, decreased levels of LH and FSH at the time of the ovulatory surge, or decreased response of the endometrium to progesterone have been implicated. Elevated prolactin levels also may be associated with luteal phase defect. The preponderance of evidence helps a preovulatory cause. Nuclear progesterone receptor concentrations are normal in luteal phase endometrial samples from women with luteal phase defect, but the concentration is reduced during the proliferative phase (suggesting an alteration, such as lesser estrogen stimulation, during the proliferative phase).

In the past, the controversies surrounding the concept of luteal phase defect have revolved around issues of diagnosis, endometrial biopsy versus progesterone levels, and treatment, progesterone versus clomiphene citrate. While space in journals and much time in postgraduate courses are devoted to these questions, a fundamental concern must be addressed. Is there really such an entity as luteal phase defect, and even if there is, does it play any role in infertility?

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A serum progesterone level of less than 3 ng/mL (10 nmol/L) is consistent with follicular phase levels. To confirm ovulation, values at the midluteal phase, just at the midpoint between ovulation and the onset of the subsequent menstrual period, should be at least 6. ng/mL (21 nmol/L) and preferably 10 ng/mL (32 nmol/L) or any more. The consensus of opinion is that a single midluteal phase progesterone level is insufficient evidence upon which to judge the adequacy of the luteal phase. The progesterone level is subject to the variation associated with pulsatile secretion, but any more importantly, there is often poor correlation with the histologic state of the endometrium.