Best Treatment for Unexplained Infertility: Ovulation Induction, or IVF?

Alice and Ted found each other later in life, and at age 38, decided to try building a family. After 6 months of trying to conceive, tests showed Alice was ovulating, had a healthy uterus, patent fallopian tubes, and sperm testing was normal, yet she did not conceive. They pondered what to do next, and asked the question - what is the best treatment for a woman with unexplained infertility in her late 30s?

They read Internet articles about an antiquated way of thinking about treatment for unexplained infertility, beginning with clomiphene and intrauterine insemination (IUI), followed by more intensive ovulation induction with injectable gonadotropins to yield more eggs. Those that were not successful went on to in vitro fertilization (IVF).

Clomiphene is a fertility pill that works by blocking estrogen receptors in the pituitary. The pituitary compensates by making more Follicle Stimulating Hormone (FSH), improving ovulation. Clomiphene is a rather mild stimulus to the ovaries, resulting in 1-4 eggs ovulated.

The more potent gonadotropins literally are FSH, which increases the number of eggs released by direct stimulation of the follicles. More eggs means more targets for the sperm, and more opportunity for conception. Multiple gestation is a common consequence, including twins, triplets, and quadruplets.

IVF takes this process several steps further, and is more efficient. Moving the eggs and sperm into the embryology lab for insemination, with transfer of a resulting embryo directly into the uterus, makes IVF a very efficient method of conception.

On the Internet, Ted and Alice learned that a randomized trial published fifteen years ago[1] showed that gonadotropin IUI was more successful than IUI or gonadotropin alone, but pregnancy rates overall were only 9% per cycle, and only a third of women conceived after 4 cycles of gonadotropin IUI. One third of those pregnancies were multiple gestations, including triplets and quadruplets.

Lucky for them, their doctor informed them of a more recent trial, the FASTT trial[2], In the FASTT trial, gonadotropin IUI did not benefit young couples with unexplained infertility that had failed clomiphene. It was less expensive to move directly to IVF after clomiphene IUI. Skipping gonadotropins and moving directly to IVF saved $9,800 per delivered child.

In older couples with declining egg health (declining ovarian reserve), are gonadotropins worth trying? A recent trial, the FORT-T study[3], looked at this issue. Couples aged 38-42 were randomized to clomiphene-IUI, gonadotropin-IUI, and IVF. Clomiphene-IUI and gonadotropin-IUI showed similar pregnancy rates, roughly 8-10 percent per cycle. IVF pregnancy rates were a little more than double the clomiphene-IUI rates. Average number of cycles to achieve pregnancy was 3.4, 3.3 for clomiphene and gonadotropin, and 1.9 cycles for IVF. At the conclusion of the trial, half of the women had delivered a baby, the majority of those from IVF.

Storing healthy euploid embryos for future use is also an option, the fertility preservation of embryos. Extra euploid embryos offer the potential for a second (or third) future pregnancy after a single oocyte retrieval. High pregnancy rates, with minimal risk, lower cost per baby delivered overall, and a shot at a 2^nd or even 3^rd child, later, from the same batch of eggs. IVF+CCS represents a tremendous advance over the previously published technologies.

At the end of the day, the most successful treatment for most couples is IVF. It allows the best opportunity to control the variables interfering with pregnancy, maximize the efficiency of reproduction, and minimize the risks associated with successful conception. Adding CCS to the IVF treatment reduces the risk of multiple gestation and miscarriage, and provides an opportunity for another child later when extra euploid embryos are obtained. IVF is faster, cheaper, and carries less risk than gonadotropin IUI.

Alice and Ted decided to proceed into IVF+CCS. At age 38, out of 12 eggs, they were able to get 2 healthy euploid embryos. Alice is pregnant after transfer of the first embryo, in a natural cycle, and has the second euploid embryo in reserve for another child a year or two down the road.

IVF+CCS is one more way Pacific Fertility Center helps build families one healthy baby at a time.

See all articles