Discovery By Fertility Specialist Offers Promise Of Reducing Multiple Births Tied To Fertility Treatment

Results of the research were presented here March 13, 1998 at the annual meeting of the Society for Gynecological Investigation.

The findings suggest that lutenizing hormone (LH), a hormone present in the second half of the menstrual cycle, may perform the critical task of sustaining the growth of egg follicles until ovulation, said Michael W. Sullivan, M.D., UB assistant professor of gynecology and obstetrics and lead researcher on the study.

They have important implications for women undergoing fertility treatments, Sullivan said, because specialists formerly thought the only way to keep a developing egg growing was to administer follicle stimulating hormone, or FSH, which also causes multiple eggs to mature.

By manipulating LH and FSH, Sullivan said it could be possible to sustain the growth and development of one or two follicles in women undergoing fertility treatment while preventing multiple ovulations and thus decreasing the risk of multiple births.

"Nobody has looked at this before, because it wasn't possible until the development of the recombinant form of the two hormones, which happened very recently," Sullivan said. "The finding is very preliminary, but it is promising."

The results are based on a prospective trial involving 24 women that Sullivan led while a fellow at the University of Pittsburgh School of Medicine.

Successful infertility treatment depends on the ability to manipulate precisely the essential hormones involved, which requires their clear identification. Infertility specialists strive for a single birth, considering anything more than twins a complication, because of the potentially serious, even life-threatening, medical problems that often accompany multiple births.

One of the stumbling blocks to this end has been identifying a way to limit the number of eggs that mature during fertility treatment while keeping at least one egg developing.

During a normal menstrual cycle, FSH stimulates egg follicles to develop. At a certain point in the cycle, estrogen signals the pituitary to stop producing FSH, a signal that at least one egg follicle is well and being nurtured. The drop in FSH stops more follicles from developing, all immature follicles die, but the "recruited" follicle lives.

"Nobody knew why the follicle continued to thrive in the face of decreased FSH," Sullivan said. "We thought that FSH was required all the way along, even at low levels. So standard procedure during fertility treatment has been to continue FSH, which keeps follicles growing, but also may stimulate too many to develop. That's the up side and down side of FSH.

"We've now shown that FSH is not essential during the entire first half of the cycle. We've discovered that LH can make up for the deficiency of FSH as the follicle grows."

Sullivan and colleagues stopped production of fertility hormones artificially in the study group, and then stimulated follicle development in all the women with recombinant human FSH. When a 14-mm. follicle was identified by ultrasound (an arbitrary size thought to guarantee sufficient maturity), the women were randomized to one of four groups: continued FSH treatment; FSH replaced with saline; FSH replaced with high dose of recombinant LH, and FSH replaced with low dose of recombinant LH.

After two days of treatment, researchers measured blood levels of estrogen, the sign that a follicle is healthy and developing normally. Estrogen levels dropped in the saline group, indicating the maturing follicle had ceased to thrive in the absence of FSH or LH. In all three remaining groups, estrogen levels continued to rise and pregnancies resulted in all three groups.

"This suggests that if you administer FSH until one follicle matures, then limit FSH and substitute LH, you can support the growth of the maturing follicle, but won't recruit any more follicles," Sullivan said. "We are now trying to determine how far back in the cycle you can push this process and still capture a maturing follicle."

Also participating in the study were Ann Stewart-Akers, Joel S. Krasnow, Sarah L. Berga and Anthony J. Zeleznik of the departments of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh School of Medicine.

The research was supported by grants from the National Institutes of Health and TAP Pharmaceuticals.