Researchers Eliminate Life-threatening Side Effect of Fertility Treatment—Ovarian Hyperstimulation Syndrome (OHSS)

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The most well-known risk from fertility treatment undertaken by over one million American females annually is a multiple pregnancy, but a more sinister and potentially fatal risk is ovarian hyperstimulation syndrome (OHSS). While OHSS can happen in a natural pregnancy, it most often happens with fertility treatments because of the hormone medications used to prompt multiple egg production (AKA superovulation). Fortunately, researchers at The Fertility Center of Las Vegas have found a way to prevent OHSS altogether. The doctors’ findings were published in July’s issue of “Fertility and Sterility” and have worldwide implications in how the fertility industry is able to increase safety for patients.

The most well-known risk from fertility treatment undertaken by over one million American females annually is a multiple pregnancy, but a more sinister risk is ovarian hyper stimulation syndrome (OHSS), states a CDC National Survey of Family Growth (1997-2002).

According to the World Health Organization, OHSS manifests with a broad spectrum of symptoms ranging from mild illness to severe disease and affects 1 percent to 5 percent of women. OHSS results from an overproduction of eggs in the ovary that can result in ovarian cyst rupture, internal bleeding, respiratory difficulties, blood clots, and can be fatal if untreated. While OHSS can happen in a natural pregnancy, it most often happens with fertility treatments because of the hormone medications used to prompt multiple egg production (AKA super ovulation). Fortunately, researchers at The Fertility Center of Las Vegas have found a way to prevent OHSS altogether. The doctors' findings were published in July's issue of “Fertility and Sterility” and have worldwide implications in how the fertility industry is able to increase patient safety.

“Even after meticulous monitoring a patient can hyper stimulate which occasionally requires hospitalization for more intensive monitoring of kidney and liver function along with IV fluid support,” says Dr. Said Daneshmand, a UCLA trained reproductive endocrinologist and researcher at The Fertility Center of Las Vegas. “Women with OHSS or ruptured ovarian cysts can hemorrhage which may require surgical intervention.” The doctor further indicates that OHSS risk increases with rising blood estrogen levels, the number of developing eggs, and when supplemental doses of human chorionic gonadotropin (HCG) are administered in the fertility treatment cycle.

Women at highest risk include those with polycystic ovarian syndrome (PCOS), a common but difficult to diagnose endocrine condition that affects women as young as 18 and usually results in excessive hair, obesity, and impaired fertility.

“We've now developed a protocol so that the highest risk patients are placed on a different medication regimen that altogether eliminating OHSS," says Dr. Daneshmand.

Included in the study was Beverly T., now a new mother and also a registered nurse who appreciated the research more than the average patient given her medical background and the fact she suffers from PCOS. She has indicated that the fertility issue was heart-wrenching enough but she also didn't want to risk complications either. Other women in the study are currently in various stages of pregnancy.

The newly elucidated medication regimen treats surging estrogen levels that are thought to contribute to the condition and the research has worldwide implications in how fertility patients are treated. The research was conducted in partnership with the University of Nevada School of Medicine for which Drs. Daneshmand and Shapiro are also faculty.

The work of Dr. Daneshmand and his partner, The Fertility Center's founder and Yale educated reproductive endocrinologist, Dr. Bruce Shapiro, were also presented at the Pacific Coast Reproductive Society in May. Their practice was the first fertility practice in southern Nevada, and is responsible for over 2,300 births. The doctors are ardent community supporters — who with their patients have donated over $30,000 to charity — and have earned consistent ratings by their peers internationally as top docs. They have also elucidated fertility treatments including blastocyst transfer, a proprietary cell medium used in IVF, and pre-implantation genetic screening.

Editor's Note: Interviews/photos with the doctors and patients part of the research are available.

Abstract - "Fertility & Sterility," July 2005

Eliminating Severe Ovarian Hyperstimulation Syndrome By Using Gnrh Agonist Instead Of Hcg

BS Shapiro,a,b ST Daneshmand, a,b FC Garner,a,b M Aguirre,a R Rossa

Fertility Center of Las Vegas and University of Nevada School of Medicine, Las Vegas, Nevada.

a Fertility Center of Las Vegas, Las Vegas, Nevada

b Department of Obstetrics and Gynecology, University of Nevada School of Medicine, Las Vegas, Nevada

Background: Ovarian hyperstimulation syndrome (OHSS) is a significant risk of controlled ovarian stimulation for IVF. Exogenous human chorionic gonadotropin (hCG) is a factor in the development of OHSS. One measure to reduce OHSS incidence includes using GnRH agonist (GnRHa) for ovulation.

Objective: This retrospective study evaluates the efficacy of GnRHa for oocyte maturation.

Materials and Methods: Patients underwent routine controlled ovarian stimulation with gonadotropins, while pituitary suppression was achieved with GnRH antagonist. Patients at significant risk for OHSS received 4 or 8 mg of leuprolide acetate when an optimal cohort of follicles was observed via ultrasound. Oocytes were retrieved 34-36h later and fertilized conventionally or by ICSI. Blastocysts were transferred after 5 or 6 days.

Results:

Thirty non-donor IVF patients with at least 20 mature follicles received ovulatory GnRHa between January 1 and October 31, 2004. From these, 889 oocytes were recovered (29.6 oocytes per stimulation), and 615 (69.2 percent) were successfully fertilized. One cycle was canceled because no viable blastocysts developed. The remaining 29 patients received 64 transferred blastocysts (mean 2.2 per transfer), and 12 intrauterine gestational sacs were subsequently observed in 9 patients, for an implantation rate of 18.8 percent and a clinical pregnancy rate of 30.0 percent.

Nineteen of these patients had supernumerary embryos frozen, seven underwent frozen embryo transfer (FET) by November 3, 2004, and six (86 percent) of these achieved clinical pregnancy.

Despite young age (mean 31.4 years, minimum 24.5 years), ample mature follicles (mean 31.2, maximum 49), and high serum estradiol (mean 4,947 pg/mL, maximum 9,977 pg/mL) on the day of ovulatory GnRHa, no patients experienced OHSS requiring aspiration of ascites.

During this period, there were seven egg-donor cycles in which the donor received ovulatory GnRHa. The donors averaged 28.3 years of age and produced a mean of 29.6 oocytes, of which 76.4 percent successfully fertilized and 35.3 percent blastulated. The donor recipients averaged 42.4 years of age. Five (71.4 percent) of these seven cycles achieved clinical pregnancy. All seven cycles had frozen supernumerary embryos. Both non-pregnant donor recipients elected FET within the study period, and one of these achieved clinical pregnancy, for a cumulative pregnancy rate of 86 percent in these donor cycles. No donors experienced OHSS requiring aspiration of ascites.

Conclusion: The use of GnRHa is a viable means of inducing oocyte maturation while avoiding OHSS in high-risk patients.

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Sharon Chayra
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