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Unexplained infertility is diagnosed when standard testing for infertility is normal following one year of unprotected intercourse. Standard workup includes a semen analysis, measurement of reproductive hormones and a hysterosalpingogram (HSG) to evaluate the uterus and the fallopian tubes. The incidence is approximately 10-20% of all infertility cases. In most incidences a specific cause can be identified with advanced testing.

Additional testing previously included documentation of ovulation by a mid-luteal progesterone level (generally one week following ovulation). However, this test is generally no longer performed because regularity of cycles almost always confirms ovulation. In patients with irregular cycles, testing for progesterone level is not necessary because these patients have irregular ovulation by history alone, which may be one of the causes of their infertility. Historic tests such as post-coital test or routine endometrial biopsy are no longer a part of standard or advanced infertility testing.

Currently, advanced testing and interventions include ovarian reserve testing, a detailed pelvic ultrasound (i.e. for ovarian cysts and fibroids), review of HSG films and evaluation of the pelvic organs by laparoscopy. In the majority of unexplained infertility cases, the cause is related to decreased egg reserve (which can be diagnosed by advanced hormone testing and a pelvic ultrasound by a fertility specialist). In other cases, HSG films need to be reviewed by an infertility expert for the presence of tubal disease. The dye may pass through the tubes on the HSG test, but this does not necessarily mean that the tubes are open or functional.

Laparoscopic evaluation may be beneficial in cases of endometriosis, abnormal HSG findings, pelvic pain, painful periods, fibroids, pelvic adhesions or the presence of endometriosis cysts (endometriomas) on pelvic ultrasound. Although additional tests are being developed to better identify the causes of infertility, none has been proven to be reliable in identifying the cause in cases of otherwise “unexplained infertility”. Certain treatment options also have been proposed, but none of these interventions have been proven to be effective either.

The chances of conceiving with unexplained infertility are 1-3% per month, compared to 10-20% for a fertile couple. These percentages are based on cumulative pregnancy rates and significantly depend on the female reproductive age. Overall pregnancy rates increase over time with additional attempts, although they tend to stay the same per attempt or cycle.

The treatment of unexplained infertility may include continuation of timed intercourse for a time period in cases of early infertility and in young couples with a completely normal infertility evaluation. In others, the first line of treatment is generally Clomid with intrauterine insemination (IUI) or injectable FSH medications with IUI. The goals of these treatments are to increase the number eggs that reach the mature stage and allow multiple ovulations (superovulation). Concurrently, injection of the sperm into the uterus (Intrauterine insemination- IUI) at the time of ovulation can be done to further increase the chances of a pregnancy. The odds are improved by increasing the number of eggs and sperm in the fallopian tubes.

Superovulation (Clomid or injectibles) and IUI is most appropriate in young couples with unexplained infertility, but the benefit may be limited in women with advanced reproductive age. This is due to the fact that ovarian reserve may be compromised (decreased number of eggs remaining in the ovaries) in some of the cases of unexplained infertility despite the presence of normal FSH and estrogen levels.

In the younger population, Clomid and IUI may increase the chances of a pregnancy up to 6-8% per cycle/attempt from a baseline rate of 1-3% (if the couple continues to try on their own). Clomid and IUI treatment can be continued up to 3-4 cycles before moving on to a more aggressive treatment with injectible FSH and IUI. This type of treatment is also continued for 3-4 cycles before a more aggressive treatment option can be considered, which is generally in vitro fertilization (IVF). The chances with injectible medications and IUI increases to 5-15% per cycle compared to 1-3% in untreated couples and 4-8% in Clomid + IUI cycles.

If none of these treatments result in a successful outcome, IVF becomes the best treatment option and results in a success rate of 50% per cycle. All of these percentages reflect the success rates in women under the age of 35 and the numbers decrease with the increasing reproductive age with all treatment options. Overall and regardless of age, IVF results in the highest pregnancy rate compared to other treatment options and is the recommend treatment for most couples with unexplained infertility.

Each case of “unexplained infertility” is unique and can be explained and treated if the exact cause is identified with advanced testing. In such cases, success rates may vary and are generally higher than true unexplained infertility. Dr. Bayrak recommends that patients seek an expert opinion when they are diagnosed with “unexplained infertility”.

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