IVF Without the Fertility Drugs

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When most people think of infertility treatment, especially in vitro fertilization, they often think of fertility medications and all that those can mean: injections, hormonal mood swings, increased chances of multiples, and greater expense.

It's true that IVF presents the best possible option toward successful pregnancy for many patients. Not all patients' bodies respond the same to fertility medication, however. For some, there's an alternative to IVF with medically- stimulated ovulation. It's called "seminatural" IVF.

Seminatural IVF cycles are nothing new, but recently published research from France shed more light on groups of women who may benefit from this form of fertility assistance. We spoke to Dr. Kristen Cain of Reproductive Specialists of New York about an option that may be news for a lot of wondering fertility patients.

What is a Seminatural IVF Cycle?

A seminatural IVF cycle (sometimes also called 'natural' cycles) is one in which the woman either uses no medication or only oral medication to prompt ovulation, then goes through egg retrieval, in vitro fertilization, and embryo transfer. This is different from a "traditional" IVF cycle in which the woman uses injectable hormones for the purpose of hyperstimulating her ovaries into ovulating more than usual, called controlled ovarian hyperstimulation (COH.)

In short, seminatural cycles have been used to meet the needs of women whose bodies do not respond well to certain fertility medications.

"The basic thought behind a seminatural cycle," explains Dr. Cain, "is that if a patient's body, even with the highest dosages of injectable medications, still only ovulates one egg, then why put her through all of the trouble? Why not try IVF without the medication?"

Cain and her colleagues have long used both unmedicated (natural) and less aggressive IVF cycles with oral fertility drugs such as clomiphene citrate or letrozole plus hCG injections to trigger release of the egg. Oral fertility medications, because they work differently from the injectable type, have the advantage of creating fewer egg follicles which in turn reduces a number of possible side effects from treatment. They are also considerably less expensive than injectable fertility drugs. The recent French study introduced the idea of a new semi-medicated protocol by including the use of a GnRH antagonist (to prevent the egg from ovulating too early) and hMG (to enhance the egg's continuing development.)

Who Can Benefit from Seminatural Cycles?

The study, conducted by physicians at ART clinics in Clamart, France, looked at using this semi-medicated IVF treatment with two groups of women: women who had "low ovarian reserve" and those who were not classified as having low ovarian reserve but who had failed to stimulate well on previous fertility medication protocols. "Ovarian reserve" refers to measurements of a woman's capacity to ovulate.

"Poor responder" is a term used to identify female fertility patients who have already tried injectable fertility medications without success (meaning their bodies didn't produce an abundance of available, good quality eggs for retrieval.) Women who are poor responders to medications often have good results from tests performed on the third day of their cycle, indicating that they probably have good ovarian reserve.

Dr. Cain helps to distinguish, "Low ovarian reserve is used to describe women who appear to be on the cusp of entering menopause early."

Only women who were 38 years old or younger were included in the study. This enabled the researchers to avoid the statistically confounding reality that groups of older women will generally show lower ovarian reserve. By including only women in the younger age range, the study was able to present a truer picture of the protocol's comparative impact on the two groups (poor responders and low ovarian reserves.)

The study's semi-medication protocol resulted in fewer IVF cycle cancellations and a relatively high implantation rate. The researchers found that if a woman is able to produce and ripen one egg but she doesn't respond well to medications to ovulate more than that, the protocol used in this study can help her get all the way to an IVF cycle.

Cancellation of an IVF cycle can be disheartening and costly, to say the least, and can occur for a number of reasons:

  • poor response to medication, that is, not ripening enough eggs
  • ovulating too early for eggs to be good quality
  • having no eggs to retrieve
  • eggs that don't fertilize
  • over-stimulation of the ovary, resulting in an unsafe condition called ovarian hyperstimulation syndrome

It might seem counterproductive to go through IVF -- the discomfort of egg retrieval, the anxiety of waiting for fertilization and then, hopefully, embryo transfer -- without the expected boost of egg production from injectable medications. But for some women, and for many reasons that are still not completely clear to researchers and physicians, even the maximum dosage of the best meds will not result in their ovulating more than one good quality egg cell.

"Often, a practitioner can have a sense for which patients will benefit from seminatural IVF prior to their going through an assisted cycle," says Dr Cain. "Cycle day 3 hormone level tests and ultrasounds to look at the ovaries can give you an idea of who has low ovarian reserves."

Another patient group that may be considered for seminatural cycles is healthy young women who are using IVF to work around purely tubal or male factor infertility. "This can be a very inexpensive protocol for someone like that," Dr. Cain explains, "because all you have to do is the egg retrieval and embryo transfer."

What Are the Benefits of a Seminatural Cycle?

Fertility medications are often the most expensive part of the IVF picture. Oral medications are usually about one-tenth the cost of injectables. So, many patients who are able to use seminatural IVF cycles will do so in order to afford the treatment.

Additionally, patients using natural and semi-natural cycles to conceive are, of course, not having to endure the same amount of uncomfortable injections and office visits for monitoring.

A reduced incidence of multiple pregnancies is a natural result of transferring fewer embryos to the woman. While many infertile couples express a desire for twins, the reality is that multiple pregnancies come with significantly higher health risks for babies and mother.

Many women report fewer hormone-related side effects from oral medications, and certainly fewer without fertility drugs.

Specific to the findings of the French study, Dr. Cain sees possibilities in her own practice. "The semi-medicated protocol that they used is an interesting variation, and I can see where it could be useful. We do run across patients who occasionally ovulate with an egg that's just too small or too immature, and this could give them that extra time for the egg to mature and be ready for fertilization."

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