Evaluation of the female for infertility
  
The strategy for female infertility evaluation has evolved into an efficient, cost- effective investigation that can usually be performed during two menstrual cycles. Invasive procedures such as hysterosalpingogram and laparoscopy are scheduled during the proliferative phase of the cycle to avoid the risk of a procedure during a concomitant pregnancy. Serum progesterone measurements are timed for 6 –8 days before the onset of menses, and endometrial biopsy is performed 2 – 3 days prior to the onset of menses. In general, hysterosalpingography, serum progesterone, is recommended during the first month. A second visit is scheduled at the conclusion of these studies to review the data and to advance to laparoscopy based on any detected abnormalities. If no explanation is discovered after these initial studies, endoscopy (hysteroscopy and laparoscopy) is performed to exclude endometriosis and nonobstructive tubal adhesions (found in approximately 50 % of cases with negative basal studies) and occult intrauterine lesions (fewer than 1 % of patients).
 
Introduction
Involuntary infertility affects about 10 – 15 % of couples of reproductive age. The causes of infertility are equally distributed between the male and the female and often the physician encounters multiple itiologies during the investigation. Most infertile couples have one or more of three major causes – a male factor, ovulatory dysfunction and tubal – peritoneal disease. Among the couple, the clinical evaluation of the female patient with reproductive dysfunction is simplified by the fact that the patient serves as her own bioassay. In the female 15 –20 % of causes of infertility are due to ovulatory dysfunction ; 30 – 40 %   due to pelvic factors such as endometriosis, adhesion, or tubal disease and 5 % due to cervical factors. The basic infertility evaluation of the female is aimed at evaluating for these disorders. Thus, the evaluation of women with infertility is an increasingly important part of strategy for infertility testing of the couple. Most of the evaluation of the female usually requires two menstruating cycles. The present article gives brief account of the evaluation work up of the female for infertility
 
Medical History
A thorough work up is based upon an extensive history and physical examination. The woman should be asked about the timing of her pubertal development and menarche. Menstrual history should include cycle length, duration and amount of bleeding, associated dysmenorrhea, and premenstrual symptoms. A history of spontaneous, regular, cyclic, predictable menses is in almost all women consistent with ovulation, while a history of amenorrhea or abnormal or unpredictable bleeding suggests an ovulation or uterine pathology. Previous pregnancies, abortions and birth control history should also be documented. The patient should be asked about dyspareunia and dysmenorrhea that may be linked to endometriosis. A history of pelvic inflammatory disease, sexually transmitted disease, and past use of an intrauterine device may be associated with tubal disease. A history of galactorrhea may be an indication of elevated prolactin levels, while a history of pubertal onset of progressive hirsutism associated with oligomenorrhea may indicate polycystic ovarian disease or other disorders of androgen excess. Excessive weight loss or gain, stress, and exercise are often associated with ovulatory disorders. Sexual, social, and psychological issues should be explored. Any prior infertility evaluation, surgery, or medical therapy is essential information and therefore records, films, or photos should be sought and carefully re-evaluated.
 
Investigations
The investigation assesses two main areas – those of ovulation and pelvic viscera normality. Ovulation is assessed first because it is less invasive and does not have the potential for morbidity that can be associated with assessment of uterine, ovarian and tubal normality.

Assessment of Ovulation
The assessment of ovulation is complex, involving history, examination and investigation. Of couples who present with infertility, 20 – 25 % will have disorders of ovulation. Pre-menstrual mastalgia, mid-cycle pain in iliac fossa and clear, stretchy, lubricative, mid-cycle mucus are some of the known symptoms of ovulation. Three procedures are used to confirm that ovulation has occurred, and two additional procedures are used to determine that ovulation will occur in the immediate future as shown in TABLE NO 1.

TABLE NO. 1
Assessment of Ovulatory Status

Test	Timing
BBT	Complete cycle
Sonography	Late follicular
LH testing	Late follicular
Serum progesterone	Mid-luteal
Endometrial biopsy	Late luteal

To determine that ovulation has occurred, most clinicians use basal body temperature (BBT) chart monitoring, luteal phase serum progesterone measurements, or secretory phase endometrial biopsy. BBT chart monitoring typically reveals a temperature below 98 degree F during the follicular phase. After ovulation the temperature rises 0.2 degree – 0.6 degree F and is sustained for 9 – 13 days during the luteal phase. Immediately before or coincident with the onset of menses, the temperature falls below 98 degree F. This typical “biphasic” profile is demonstrated repeatedly in ovulatory women. Use of BBT chart monitoring to determine dysfunctional ovulation (in contrast to the absence of ovulation) is generally not helpful. Unfortunately, parameters such as the number of temperature –elevated days and the magnitude of the temperature rise have correlated with other measures of luteal function (progesterone, endometrial biopsy) and have not been used reliably to initiate therapy. Thus, BBT chart monitoring can establish ovulation but is unable to determine the presence or absence of ovulatory disturbances. Serum progesterone concentrations are higher than 5 ng / ml during the luteal phase. Most clinicians use the luteal phase progesterone level to establish both ovulation and the quality of ovulation. If the serum progesterone is higher than 5 ng / ml, ovulation is confirmed. This measurement can apply to any day of the luteal phase. When more rigorous criteria are set for the time of progesterone measurement (6 – 8 days prior to the onset of menses – typically day 20 –22 of the cycle), several investigators have reported that the “quality” of ovulation can be determined. The precise threshold value of progesterone is controversial, but most agree that a mid- luteal progesterone level of less than 10 ng / ml is consistent with luteal dysfunction. Additionally, most authors agree that a serum progesterone level higher than 20 ng / ml is consistent with adequate luteal function. There is no consensus on what a serum progesterone level of 10 – 20 ng / ml indicates about luteal function, but it clearly means that ovulation has occurred. Endometrial biopsy is typically performed during the late luteal phase to classify the morphologic transformation of the secretory endometrium. The “luteal phase defect” has been defined as endometrium that is more than 48 hours “out of phase” with the cycle. The proper interpretation of this test requires three pieces of information:

1. The date the test was performed.
2. The date natural menstruation occurred. 
3. The morphologic dating of the endometrial specimen.

For example, a specimen obtained on day 26 of a 28 – day cycle that was interpreted as consistent with day 23 endometrium would be considered out of phase, but a specimen obtained 6 days before the onset of menstruation consistent with day 23 secretary endometrium would be considered in phase. Finally, interest has emerged concerning adjunctive measurement of endometrial peptides. In particular, some integrins are known to be expressed at unique times during the secretory phase. Measurement of these factors may increase the accuracy of properly classifying endometrial specimens. Unfortunately, there is a mixed degree of agreement regarding serum progesterone measurements and endometrial maturity. Hence, these two tests currently stand at the “discretion of the practitioner” as independent but not correlated tests. Follicular measurements by sonography have been used to predict ovulation. In general, a naturally growing follicle expands at approximately 2 –3 mm per day and ruptures after the follicular diameter approaches 20 –22 mm. After rupture the follicle generally collapses, and fluid collects in the cul-de-sac. Commonly, a luteal structure can be observed in the ovary. Finally, urinary measurements of mid-cycle luteinizing hormone (LH) can detect the preovulatory LH surge. Because urinary LH measurements are done infrequently (usually once or twice daily), it is reasonable to estimate that ovulation will occur 24 –36 hours after detection of the surge.

The abnormalities of ovulation must be assessed for their cause. The direction of assessment  is formulated from the history and examination findings. Polycystic ovarian disease (PCOD) may be associated with abnormalities of ovulation and luteal phase defect. Diagnosis depends on an ultrasound examination demonstrating greater than 10 to 15 follicles in each ovary, raised androstenedione and testosterone levels, with an LH, FSH ratio greater than 2 : 1. In the presence of the galactorrhoea, the prolactin level is almost invariably elevated, and if this elevation is twice the upper limit of normal, both the follicular and luteal phases are usually abnormal and often oligomenorrhoea or amenorrhoea is present.

Assessment of Pelvic Viscera
Clinical pelvic examination will alert the physician to gross abnormalities, by noting both abnormal masses attached to or separate from the uterus or ovaries, or reduced mobility of these structures. Abnormal discharge or undue tenderness may raise the question of pelvic inflammatory disease, endometriosis or ovarian cysts. Two principal anatomic defects deserve evaluation for couples with infertility. Uterine abnormalities (malformations, uterine fibroids, endometrial polyps) and tuboperitoneal factors (pelvic scarring from infection or prior surgery, endometriosis, congenital tubal abnormalities) can be evaluated by several techniques (Table No.2).

(TABLE  NO. 2)
Assessment of Tubopeitoneal / Anatomic Status

Test	Comment
Hysterosalpingography	High false-negative rate
Laparoscopy	Confirms peritoneal disease
Hysteroscopy	Confirms intrauterine disease
Sonohysterography lesions	Visualizes mural and intrauterine
Sonography contour	Identifies uterine and endometrial

A time- honored test for evaluating uterine and tubal factors is hysterosalpingography. It is a contrast study performed under fluoroscopy, where radiopaque solutions are injected into the uterus to define the outline of the uterus and fallopian tubes. If the hysterosalpingogram is normal (normal uterine contour with bilateral tubal fill and spill), it has a negative predictive value of only about 60%. This is principally because the infertility population has a high incidence of endometriosis, which typically represents peritoneal disease but not tubal disease. Therefore, the tubes appear open on the hysterosalpingogram, but the disease remains unrecognized by this limited study. Similarly, proximal tubal occlusion has a 50 % positive predictive value. At the time of further diagnostic studies proximal tubal occlusion cannot be demonstrated, probably related to the presence of tubal spasm or another technical problem associated with the procedure. However, the hysterosalpingogram has a high positive predictive value if distal tubal occlusion is detected. When distal tubal occlusion is detected, untreated patients are at increased risk for pelvic infection. Therefore, these patients should be treated with an outpatient course of antibiotics. Sonography is a valuable tool for detecting uterine structural lesions such as uterine fibroids and adnexal pathology. Although the role of sonography has been limited by its inability to evaluate tubal status and subtle abnormalities of the endometrium (polyps, small fibroids), it is emerging as a relatively simple OPD procedure that can provide the clinician with extra details concerning the pelvic anatomy. The inclusion of sonohysterography has explained our view of the endometrium to detect intrauterine abnormalities that may go undetected. However, even with sonohysterography, demonstration of tubal patency is difficult. Despite, the problems, sonography and sonohysterography currently are best applied to the evaluation of the uterus and endometrium.

Endoscopy is currently considered the most thorough, comprehensive tool for evaluating pelvic anatomy. Laparoscopy allows visualization of the peritomeum to detect endometriosis and to assess tubal status. Hysteroscopy can be used to evaluate the endometrium and the tubal ostia. Additionally, when disease is detected, therapy can be provided. These therapies include adhesiolysis, neosalpingostomy, and adnexal surgery. Tubal lesions can be grouped in two major groups : distal and proximal tubal diseases. Proximal tubal obstruction occurs less frequently that distal obstruction and its etiology and treatment are more controversial as given in TABLE NO.3.

TABLE NO.3
ETIOLOGIES OF PROXIMAL AND DISTAL TUBAL DISEASE

Distal Tubal Obstruction Hydrosalpinx (thin / thick walled ; hydrosalpinx simplex / follicularis) Pelvic inflammatory disease Proximal Tubal Obstruction Congenital atresia Debris, viscous secretions Muscular spasm, stromal edema Obliterative fibrosis Salpingitis isthmica nodosa Chronic tubal inflammation Intrinsic (intramural) endometriosis Endosalpingiosis Tubocornual polyps Granulomatous salpingitis (genital tuberculosis, actinomycosis, schistomsomiasis, sarcoidosis, foreign bodies) Remnants of ectopic pregnancy Tubal sterilization

Even after thorough investigation, 10 percent of couples will lack a distinct diagnosis of their cause(s) of infertility. A complete review of the couple’s evaluation is warranted to assure no oversights; a repeat history may reveal sexual dysfunction, nonproductive timing of intercourse, or the use of spermicidal agents as lubricants. Borderline test results may need to be repeated. Assuming satisfaction with the couple’s evaluation, aperiod of expectant management will result in pregnancy in some couples. Artificial insemination techniques may then be elected. In vitro fertilization and gamete intrafallopian transfer are the final options for the couple with unexplained infertility.

Clinical Focus

• Routine screening of infertile women for anemia, blood grouping, antibody status though not mandatory but are extremely helpful prior to diagnosis and therapy of their infertility.
• Basal body temperature charting, sonographic follicular monitoring, urinary LH testing, and mid-luteal progesterone levels are important tests to evaluate ovulation and subsequent corpus luteum function. 
• Initial medical history of women compatible with polycystic ovarian disease (PCOD), oligomenorrhea, or amenorrhea associated with weight loss or excessive obesity, exercise, eating disorders and galactorrhea are helpful indicators of ovulatory dysfunction.
• Hysterosalpingography (HSG) provides information regarding the shape of the uterine cavity and patency of the fallopian tube whereas laproscopic intervention helps in identifying infertility factors such as endometriosis, pelvic adhesions and uterine leiomioma.

Conclusion
About half of couples who experience difficulties conceiving do so as the result of female infertility. Most causes of female infertility can now be identified through testing. A general state of health, lifestyle pattern, and medical and menstruation history is often helpful before specific investigation for the diagnosis of female infertility is initiated. By measuring the levels of FSH on day 3 of cycle, clinician can get an indication of how close a woman is to menopause and whether she has any ovarian reserve. Pre-menstrual molimina, basal body temperature, mid-cycle mucus changes, plasma progesterone, urinary LH levels and ultra sound follicle tracking are some of the tests which can assess ovulation in women. Once preliminary tests show that the woman is ovulating, a battery of more advanced tests is employed to identify the cause of woman’s infertility. These tests investigate the condition and functioning of hormones, ovaries, uterus and fallopian tubes of the woman. The use of laproscope and hysteroscope which enables the direct visualization of the pelvic viscera helps identify uterine and tubal abnormalities of the infertile woman.