Drugs for Inhibiting Uterine Contractions After IVF Studied

AMSTERDAM — Two drugs that inhibit uterine contractions might provide a novel approach to improving implantation rates in patients undergoing IVF, according to early research reported at the annual meeting of the European Society of Human Reproduction and Embryology.

“Contractions of the uterus are more frequent in IVF cycles compared to normal menstrual cycles, and a higher frequency of contractions around the time of embryo transfer is associated with a more negative impact on pregnancy outcomes,” reported Dr. Christophe Blockeel of the center for reproductive medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium.

“We've learned that uterine contractions are actually in many cases expelling somewhere between 15% to 50% of embryos after transfer,” commented Roger Pierson, Ph.D., a collaborator in the study, and professor of obstetrics, gynecology, and reproductive sciences at the University of Saskatchewan (Sask).

“Regardless of which catheter you use, or whether or not you use ultrasound, you are still irritating the uterus and it doesn't matter how gentle you are, some women are going to respond with advanced uterine contractions,” he said in an interview.

The study, which was conducted in oocyte donors and was funded by Ferring Pharmaceuticals, examined the effect of the selective oxytocin antagonist barusiban and the mixed oxytocin/vasopressin antagonist atosiban versus placebo on luteal phase uterine contractions.

The study participants were 125 oocyte donors who had undergone controlled ovarian stimulation, oocyte retrieval, and luteal phase supplementation with progeste progesterone. Women were randomized to either barusiban (41 women, IV bolus 9 mg, IV infusion 2.16 mg/h); atosiban (42 women, IV bolus 6.75 mg, IV infusion 18 mg/h); or placebo on day 2 after oocyte retrieval.

Transvaginal ultrasounds lasting at least 5 minutes were obtained after retrieval on day 1, 14 times on day 2 (pretreatment, 8 times before mock embryo transfer, 3 times after mock embryo transfer, and 2 times post infusion), and on Day 5.

With both medications, the frequency of uterine contractions remained stable during the first 2 days after retrieval, followed by a significant decrease noted in both treatment groups that lasted for about 3 hours.

“These medications are quite short acting, so they need to be administered an hour or two before transfer just to get the uterus settled to facilitate implantation,” explained Dr. Pierson, who is also a consultant for Ferring.

Without the control medication the frequency of uterine contractions can be as high as 6 or 7 per minute after embryo transfer, he said, adding that the ideal is somewhere around 1 to 1.5 contractions per minute.

“This is a very new approach to improving implantation and quite different,” he explained. While atosiban is already used to treat preterm labor, barusiban was specifically developed to treat uterine contractions in IVF, and another similar medication is being developed by the company.

“Both barusiban and atosiban are very well tolerated drugs; however, toxicology tests are still needed before we can use these drugs in patients undergoing embryo transfer rather than donors,” Dr. Blockeel said. Optimal dosing also needs further investigation.

AMSTERDAM — Two drugs that inhibit uterine contractions might provide a novel approach to improving implantation rates in patients undergoing IVF, according to early research reported at the annual meeting of the European Society of Human Reproduction and Embryology.

“Contractions of the uterus are more frequent in IVF cycles compared to normal menstrual cycles, and a higher frequency of contractions around the time of embryo transfer is associated with a more negative impact on pregnancy outcomes,” reported Dr. Christophe Blockeel of the center for reproductive medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium.

“We've learned that uterine contractions are actually in many cases expelling somewhere between 15% to 50% of embryos after transfer,” commented Roger Pierson, Ph.D., a collaborator in the study, and professor of obstetrics, gynecology, and reproductive sciences at the University of Saskatchewan (Sask).

“Regardless of which catheter you use, or whether or not you use ultrasound, you are still irritating the uterus and it doesn't matter how gentle you are, some women are going to respond with advanced uterine contractions,” he said in an interview.

The study, which was conducted in oocyte donors and was funded by Ferring Pharmaceuticals, examined the effect of the selective oxytocin antagonist barusiban and the mixed oxytocin/vasopressin antagonist atosiban versus placebo on luteal phase uterine contractions.

The study participants were 125 oocyte donors who had undergone controlled ovarian stimulation, oocyte retrieval, and luteal phase supplementation with progeste progesterone. Women were randomized to either barusiban (41 women, IV bolus 9 mg, IV infusion 2.16 mg/h); atosiban (42 women, IV bolus 6.75 mg, IV infusion 18 mg/h); or placebo on day 2 after oocyte retrieval.

Transvaginal ultrasounds lasting at least 5 minutes were obtained after retrieval on day 1, 14 times on day 2 (pretreatment, 8 times before mock embryo transfer, 3 times after mock embryo transfer, and 2 times post infusion), and on Day 5.

With both medications, the frequency of uterine contractions remained stable during the first 2 days after retrieval, followed by a significant decrease noted in both treatment groups that lasted for about 3 hours.

“These medications are quite short acting, so they need to be administered an hour or two before transfer just to get the uterus settled to facilitate implantation,” explained Dr. Pierson, who is also a consultant for Ferring.

Without the control medication the frequency of uterine contractions can be as high as 6 or 7 per minute after embryo transfer, he said, adding that the ideal is somewhere around 1 to 1.5 contractions per minute.

“This is a very new approach to improving implantation and quite different,” he explained. While atosiban is already used to treat preterm labor, barusiban was specifically developed to treat uterine contractions in IVF, and another similar medication is being developed by the company.

“Both barusiban and atosiban are very well tolerated drugs; however, toxicology tests are still needed before we can use these drugs in patients undergoing embryo transfer rather than donors,” Dr. Blockeel said. Optimal dosing also needs further investigation.

AMSTERDAM — Two drugs that inhibit uterine contractions might provide a novel approach to improving implantation rates in patients undergoing IVF, according to early research reported at the annual meeting of the European Society of Human Reproduction and Embryology.

“Contractions of the uterus are more frequent in IVF cycles compared to normal menstrual cycles, and a higher frequency of contractions around the time of embryo transfer is associated with a more negative impact on pregnancy outcomes,” reported Dr. Christophe Blockeel of the center for reproductive medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium.

“We've learned that uterine contractions are actually in many cases expelling somewhere between 15% to 50% of embryos after transfer,” commented Roger Pierson, Ph.D., a collaborator in the study, and professor of obstetrics, gynecology, and reproductive sciences at the University of Saskatchewan (Sask).

“Regardless of which catheter you use, or whether or not you use ultrasound, you are still irritating the uterus and it doesn't matter how gentle you are, some women are going to respond with advanced uterine contractions,” he said in an interview.

The study, which was conducted in oocyte donors and was funded by Ferring Pharmaceuticals, examined the effect of the selective oxytocin antagonist barusiban and the mixed oxytocin/vasopressin antagonist atosiban versus placebo on luteal phase uterine contractions.

The study participants were 125 oocyte donors who had undergone controlled ovarian stimulation, oocyte retrieval, and luteal phase supplementation with progeste progesterone. Women were randomized to either barusiban (41 women, IV bolus 9 mg, IV infusion 2.16 mg/h); atosiban (42 women, IV bolus 6.75 mg, IV infusion 18 mg/h); or placebo on day 2 after oocyte retrieval.

Transvaginal ultrasounds lasting at least 5 minutes were obtained after retrieval on day 1, 14 times on day 2 (pretreatment, 8 times before mock embryo transfer, 3 times after mock embryo transfer, and 2 times post infusion), and on Day 5.

With both medications, the frequency of uterine contractions remained stable during the first 2 days after retrieval, followed by a significant decrease noted in both treatment groups that lasted for about 3 hours.

“These medications are quite short acting, so they need to be administered an hour or two before transfer just to get the uterus settled to facilitate implantation,” explained Dr. Pierson, who is also a consultant for Ferring.

Without the control medication the frequency of uterine contractions can be as high as 6 or 7 per minute after embryo transfer, he said, adding that the ideal is somewhere around 1 to 1.5 contractions per minute.

“This is a very new approach to improving implantation and quite different,” he explained. While atosiban is already used to treat preterm labor, barusiban was specifically developed to treat uterine contractions in IVF, and another similar medication is being developed by the company.

“Both barusiban and atosiban are very well tolerated drugs; however, toxicology tests are still needed before we can use these drugs in patients undergoing embryo transfer rather than donors,” Dr. Blockeel said. Optimal dosing also needs further investigation.