Transatlantic Team Finds Potential Cause of Fertility Treatment Side Effect

Posted September 30, 2003


FOR IMMEDIATE RELEASE - September 29, 2003 2003-09-27-ME

Transatlantic Team Finds Potential Cause of Fertility Treatment Side Effect

University of Saskatchewan reproductive experts and their European
colleagues have discovered a genetic mutation that may cause "ovarian
hyperstimulation syndrome" (OHSS) in women -- a potentially life-threatening
side effect of fertility treatment.

OHSS can vary in seriousness from ovarian enlargement with slight abdominal
pain and discomfort to potentially life-threatening massive ovarian
enlargement that causes hormones and fluid to leak from the ovaries into the
abdominal cavity and chest.

The study - based on the unusual case of a Saskatchewan woman who developed
spontaneous OHSS during each of four pregnancies -- was recently published
in the prestigious New England Journal of Medicine.

"This research should allow development of a screening test for OHSS and
hopefully a potential therapy," said Roger Pierson, a member of the research
team and director of the U of S Reproductive Biology Research Unit. "That's
still a long way off, but we have a good place to start looking now."

The syndrome is usually experienced by women taking drugs that mimic natural
female hormones to stimulate ovary production. Less than one per cent of
women who undergo fertility treatment experience severe forms of OHSS. Up to
20 per cent of women undergoing such treatment experience mild forms of the
syndrome. In pregnant women, OHSS usually worsens, potentially putting the
woman's life at risk.

The Saskatchewan woman in the study was not on hormone therapy when she
developed the syndrome. Her case was initially published in an international
obstetrics journal by U of S obstetrics department head Femi Olatunbosun and
colleagues in 1996.

The article generated world-wide interest and the U of S team was contacted
by a research group from Belgium with the innovative idea that this syndrome
might be caused by a mutation in the receptor for FSH.

"This idea came from Gilbert Vassart's research group in Belgium whose lab
is one of the world leaders in research on the molecular aspects of
endocrine diseases and conditions," Pierson said. Other members of the
Belgium team include Guillaume Smits, Anne Delbaere, and Sabine Costaliola.

Gene sequencing revealed a mutation in the woman's follicle-stimulating
hormone (FSH) receptor -- a receptor that helps control the menstrual cycle
and ovarian egg production in response to the release of the FSH hormone
from the pituitary gland.

The patient's FSH receptors were responding to a hormone produced by the
developing embryo, rather than by her own body. "The ovaries responded in a
very dramatic fashion, swelling to more than 10 times their normal size and
leaking fluid," said Pierson.

Olatunbosun, associate professor Donna Chizen, and Pierson monitored the
pregnancy through ultrasounds and blood tests, using abdominal punctures to
remove excess fluid from the abdomen. At full term, the patient gave birth
to a healthy boy.

Of the three spontaneous OHSS cases reported in the medical literature, she
was the first to deliver a healthy baby. The other two women with the
condition were subjected to therapeutic abortion after the syndrome put
their lives in grave danger.

Armed with the knowledge that a genetic mutation can cause the problem, the
team plans to study women who experience OHSS following fertility therapy to
see what may cause or predispose them to the condition.

Funding for the research was provided by four Belgian research agencies -
the Service for Sciences, Technology, and Culture, the Fonds de la Recherche
en Sciences et Médecine, the Fonds National de la Recherche
Scientifique, and the Association Recherche Biomédicale et
Diagnostic, as well as the Canadian Institutes for Health Research.

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For more information, contact:

Olufemi Olatunbosun
Obstetrics, Gynecology and Reproductive Sciences
University of Saskatchewan
(306) 966 8033

Roger Pierson
Reproductive Biology Research Unit
University of Saskatchewan
(306) 966-4458

Kathryn Warden
Research Communications
University of Saskatchewan
(306) 966-2506
kathryn.warden@usask.ca
www.usask.ca/research