A 38-year-old woman and her 47-year-old husband are trying to have a child. This is the 2nd marriage for both of them. She has 1 child and he has 2 children by former marriages. They remarried 13 months ago.

The wife has been surfing the internet for information about in-vitro fertilization (IVF). She has come across several fertility clinics that make it all sound so easy: "Take home a baby or we will refund 70% of your money-No risk!" She is overly optimistic that they will be able to have a baby with these methods.

Questions:

6.1 What should the physician take into consideration when talking to the couple about their chances of having a baby with IVF?

Due to many different factors (e.g., sensationalized IVF success stories in the media, unrealistic promises from fertility clinics, beliefs that women can easily have a baby at any age), many women tend to think their own personal chances of having a baby through assisted reproductive techcnologies are higher than they actually are. Remember that assisted reproduction is not covered by insurance, but is "private pay" and therefore a lucrative "for profit" business activity by these clinics.

When talking with couples about their chances of success, it is important to present statistics on the percentage of women who will actually have a baby, rather than the percentage that will become pregnant. Fertility clcinics often report percents of successful pregnancies rather than births resulting from treatment, which tends to exaggerate the success rates. The higher likelihood of multiple pregnancies (due to multiple embryo transfer, which increases the odds for the clinic, but also increases the risk for pre-term deliveries and infant death among multiple births) also exaggerates the success rate figures. At the beginning of infertility treatment, couples are more likely to fucus on success rates than failure rates. Thus, it is important to dicsuss with them the high likelihood of failure, despite the optimistic claims of the fertility clinics.

6.2 What conditions should be considered before jumping directly to IVF?

An estimated 10-15% of couples in the U.S. meet criteria for infertility after trying to conceive for 1 year. Without treatment, 23% of couples conceive within 2 years and 10% more conceive within 4 years, so after 4 years, a third of infertile couples will conceive without medical intervention.

Thus, 1 in 25 American men has an infertility problem. In 90% of cases of male infertility, there is azoospermia, oligospermia, or abnormal sperm. Despite a sperm count below 2 million per cc, about 1 in 12 couples will conceive within 2 years. Causes include chromosomal abnormalities (XXY, XYY), prior infection (mumps), pituitary problems (prolactinoma), and varicocele, among others.

In women, there can be pituitary (prolactinoma), ovarian (failure, abscess, torsion, endometriosis), tubal (pelvic inflammatory disease), and endometrial (abnormal cycles, leiomyoma, adenomyosis) problems.

Since both partners have had a prior conception, genetic or developmental problems are unlikely. Of course one should always take a complete history, including a drug history.

Additional history:

On physical examination, she is 162 cm tall and weighs 65.6 kg. Her vital signs are: T 38.1 C, P 105/min, RR 20/min, and BP 140/80 mm Hg. There are no remarkable findings except for a fine tremor of her outstreched hands. Review of systems reveals that she has been trying to lose weight over the past year, and has lost 4 kg. She has been bothered by occasional diarrhea during the past year.

On physical examination, he is 178 cm tall and weighs 95 kg. His vital signs are: T 37 C, P 79/min, RR 15/min, and BP 135/85 mm Hg. There are no major findings on physical examination. An orchidometer is used to estimate the testicular volume, which is greater than 20 cc on the right and <20 cc on the left. Review of systems reveals that he has had exertional angina for the past 3 years, for which he was prescribed a "heart pill".

6.3 What do you make of these findings?

Her findings suggest hyperthyroidism. On asking her again, you find that she has been taking thyroid hormone, which she does not consider a "drug" when you asked about drugs she was taking. She has been taking the thyroid hormone to lose weight. If you were to check, you would find that her serum free thyroxine was 7.5 ng/mL (normal 0.8 - 1.8 ng/mL) and her TSH 0.2 mU/mL (normal 0.4 - 5.0 mU/mL).

Causes for unilateral testicular atrophy include vascular and infectious etiologies. An ultrasound is performed which reveals a varicocele on the left.

The man does not, of course, have the "heart pills" with him, so he calls you upon returning home and looking at the bottle and reading off, "d-i-l-t-i-a-z-e-m." ®

6.4 What should you do next?

The woman should not be taking the thyroid medication, and she can taper that off. He can be re-evaluated to determine if he needs the calcium channel blocker, or a substitute may be found for the diltiazem.

Additional history:

After 6 more months, she has had short or irregular menstrual cycles. He feels as though he has more energy.

6.5 How could you tell if she is going through menopause? What do you do next?

Her LH and FSH levels are not high, as they would have been with menopause. Her progesterone level is borderline low. An endometrial biopsy is performed and shows changes consistent with an inadequate luteal phase. An inadequate luteal phase, or luteal phase defect, results from inadequate progesterone during the menstrual cycle. This results in a lag of more than two days in the development of the endometrium, as dated by the histologic appearance of the biopsy. A luteal phase defect may affect 1 in 25 infertile women, but it can be found in up to a third of isolated cycles of normal women.

Have you forgotten about him? Have we gotten a sperm count with morphology yet? His sperm count is 3 million, with >95% motile, morphologically normal sperm.

6.6 What can you do next?

For an inadequate luteal phase, progesterone injections or gel may be used. If the FSH is low then clomiphene citrate may also be used. Up to half of women may conceive following this therapy. The risk of using clomiphene citrate is its uncertain effectiveness and a 5% chance of multiple births (mostly twins).

Given the low sperm count, a testicular ultrasound can be performed. He has a varicocele, which is the abnormal dilation of the veins of the pampiniform plexus of the scrotum. Varicoceles are present in a sixth of men and in a third of infertile men. It is the most common cause for surgically correctable male infertility. Varicoceles may affect spermatogenesis and/or steroidogenesis. Indications for repair include a varicocele with infertility, or a symptomatic varicocele.