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Daniel
A. Potter, MD, FACOG
Board
Certified, Reproductive Endocrinologist
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.
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. An FSH level alone is never useful and should
always be accompanied by an estradiol (E2) level. 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. See
the page on the clomiphene citrate challenge test.
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 t3o administer.
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 2 hour glucose tolerance
test with insulin levels. A glucose to insulin ratio
of >4.5 being normal. Routine testing of patients
that don’t meet these criteria is not useful. Patients
with abnormal insulin to glucose ratio should be referred
to a reproductive endocrinologist for further evaluation.
Additional Fertility Tests
In summary, the contemporary
fertility evaluation should be both thorough and
rapidly accomplished. All aspects of both the female
and male reproductive systems should be considered.
The workup should be completed within a single menstrual
cycle if at all possible. Referrals to sub-specialists
should be made when appropriate. Some referral guidelines
are listed below:
Factors Warranting Referral to
a Reproductive Endocrinologist Fertility Specialist
Factors Warranting Referral to a Urologist
- Male sexual dysfunction
- Abnormal male physical findings
- Azoospermia
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