The Female Evaluation

The infertility workup of the female partner has undergone several changes over the years but the basics have remained the same. The well-orchestrated female workup can be completed in a single menstrual cycle. At the end of this workup, along with the male data, the clinician should be able to plot a definitive course of treatment. The workup will be divided between female patients who are ovulatory by history and those that are not. Ovulation is presumed if the female has had regular menses every 26-32 days for the last six months. It is important to organize the workup to prevent unnecessary testing. The female workup should start with an initial intake that includes a thorough history, physical examination and a transvaginal pelvic ultrasound. Important historical details include those that might indicate previous exposure to STDs (such as a history of abnormal pap smears), recurrent pregnancy loss and the duration of infertility. Physical examination and pelvic ultrasound will identify patients that have gross pathology requiring surgical treatment prior to further fertility evaluation. For example, a dermoid cyst requiring surgery would allow the surgeon to evaluate tubal patency at the time of surgery rather than ordering an HSG.

Ovarian Reserve Testing
After the initial intake, the next step in the evaluation of the ovulatory female is the evaluation of ovarian reserve. The level of ovarian reserve and the age of the female partner are the most important prognostic factors in the fertility workup. Ovarian reserve is evaluated with a cycle day three FSH and estradiol level. On the third day of bleeding, a simple blood test yields a lot. Normal ovarian function is indicated when the FSH is <10 mIU/mL and the estradiol is <65 pg/mL. If the FSH is >15 mIU/mL, the patient will require egg donation. If the FSH is 10-15 mIU/mL or the E2 is >65 pg/mL, the more sensitive clomiphene citrate challenge test (CCCT) should be performed to further define ovarian reserve.

Tubal Patency
The next step in the ovulatory patient is to confirm tubal patency. This has been done traditionally with the hysterosalpingogram (HSG) and nothing has really improved on this. The HSG is performed at the outpatient radiology department. It involves injecting dye into the uterus and monitoring its "flow back" through the fallopian tubes. Blockages appear as concentrations of dye at the point of the obstruction. This test should be done in the follicular phase of the cycle after bleeding has stopped and before possible ovulation. The ordering physician should personally review the films to confirm findings of the study. Loculation of spill and tubal phimosis indicate that laparoscopy may be helpful. If large hydrosalpinges are identified, they should be clipped or removed laparoscopically prior to in vitro fertilization. Several large studies as well as a recent metanalysis, have confirmed the pregnancy rates with IVF are reduced by half in the presence of hydrosalpinges and that the rates are normalized with salpingectomy. The exact etiology of the phenomenon is not known.

Confirmation of Ovulation
Confirmation of ovulation is unlikely to be helpful in women when a careful history is consistent with ovulation. If there is doubt, a cycle day 21 progesterone with a level greater than 4 ng/mL is indicative of ovulation with most conceptions cycles having levels greater than 10 ng/mL. Alternately, sonographic confirmation of follicle rupture with serial ultrasound can be performed. Some programs use the basal body thermometer (BBT) to predict ovulation. The BBT measures the slight rise in temperature that occurs immediately prior to ovulation. Most physicians prefer to use the urinary ovulation predictor kits as they are more accurate and easy to administer.

Anovulatory Patients
The apparently oligomenorrheic patient should have the cause of their anovulation evaluated thoroughly prior to the initiation of treatment. The initial physical examination should note the presence or absence of goiter, acanthosis nigricans, striae, normal secondary sexual characteristics, Turner’s stigmata, galactorrhea, hirsuitism and abnormalities of the reproductive tract. Ultrasound should note the thickness of the endometrial lining as well as whether the ovaries are polycystic in nature. An endometrial biopsy should be considered if the uterine lining measures greater than 15mm.

Endocrine Evaluation
In anovulatory patients, the initial laboratory evaluation should include random levels of FSH, LH, prolactin, TSH, DHEAS and testosterone. Insulin resistance should be considered in patients that have any of the following: obesity, hirsuitism or acanthosis nigricans on physical exam; polycystic ovaries on ultrasound; inverted FSH/LH ratio or androgen excess on laboratory examination. Evaluation for insulin resistance can be accomplished simply with a 12 hour fasting serum insulin level. A 12 hour fasting serum insulin level of more than 10 mIU/ml signifies hyperinsulinemia in that PCOS subject.

Fertility Tests

Laparoscopy
The laparoscopy is a common outpatient surgical procedure that allows the physician to view reproductive organs such as the tubes, ovary, and uterus, and diagnose conditions causing infertility including endometriosis and tubal blockage(see picture). The laparoscope is a small "telescope like" instrument that is placed through a small incision in the abdomen, usually at the belly button(see picture). Small operative tools are inserted through another small incision at the pubic hairline. The laparoscope usually does not produce noticeable scarring. The abdomen is filled with gas causing it to expand making the internal organs more accessible. Reproductive surgeons undergo extensive advanced microsurgical training with the laparoscope. They are able to perform many, if not most, fertility operations using the laparoscope, which dramatically reduces recovery time, pain cost, and adhesions/scarring. Fertility specialists will usually treat conditions such as endometriosis during the diagnostic laparoscopy. This is one reason that a specialist should perform the laparoscopy when infertility is suspected.

Hysteroscopy
The hysteroscopy is an important tool in the study of infertility, recurrent miscarriage, or abnormal uterine bleeding. Diagnostic hysteroscopy is used to examine the inside of the uterus, also known as the uterine cavity, and is helpful in diagnosing abnormal uterine conditions such as internal fibroids, scarring, polyps, and congenital malformations(see picture). A hysterosalpingogram (an x-ray of the uterus and fallopian tubes) or an endometrial biopsy may be performed before or after a diagnostic hysteroscopy. The first step of diagnostic hysteroscopy involves slightly stretching the canal of the cervix with a series of dilators. Once the cervix is dilated, the hysteroscope, a narrow lighted viewing instrument, similar to but smaller than the laparoscope, is inserted through the cervix and into the lower end of the uterus(see picture). Carbon dioxide gas or special clear solutions like normal saline or glycine are then injected into the uterus through the hysteroscope. This gas or solution expands the uterine cavity, clears blood and mucus away, and enables the physician to directly view the internal structure of the uterus. Diagnostic hysteroscopy is usually conducted at Rotunda under propofol anesthesia. Diagnostic hysteroscopy is usually performed soon after menstruation because the uterine cavity is more easily evaluated and there is no risk of interrupting a pregnancy. A mock transfer or trial transfer may also be done at this time.

Ultrasound
Ultrasound measurements have many applications in the infertility evaluation and are also used for monitoring during in vitro fertilization stimulation cycles. The transvaginal ultrasound (through the vagina) is used frequently because it allows the physician to view the ovaries, uterus, and many other internal organs. The ultrasound produces images similar to an x-ray; however, sound waves are used instead of radiation. Many times dense structures, such as uterine fibroids, are clearly visible on transvaginal ultrasound. The ultrasound is also able to show the follicles on the ovaries as they develop and are ovulated(see picture). The fertility specialist must know the number and size of the follicles during drug-stimulated IVF cycles as this information helps in adjusting medication dosages. Ultrasound is used to measure the width of the endometrium, which must thicken and become more vascular to accept a developing embryo(see picture). It is also used as a means to document pregnancy by visualizing the fetal heartbeat.