From the Journals

High-dose progesterone to reverse mifepristone held still 'experimental'

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Study emphasizes the significance of scientific rigor

I think that this study highlights the importance of scientific rigor approved by an institutional review board when we counsel and care for our patients. As ob.gyns., we have to remember the privilege that women entrust us with their health and well being. To a certain extent, we also care for their families within our scope of reproductive health. We practice based on the best evidence available and consider referral to another trusted provider when we feel that we cannot provide unbiased care. I also feel obligated to share my opinion that legislators should trust the scientific and clinical community to not only prioritize women and their health, but also avoid introducing legislation that infringes on medicine.

Dr. Catherine Cansino is an associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis.

Dr. Catherine Cansino

I applaud the investigators for the innovation of the study design and complying with their ethical duty to terminate the study early given safety concerns. I also appreciate the authors’ transparency in presenting outcomes for all subjects. Other case reports on this topic have presented only positive outcomes (i.e., continuing pregnancies/deliveries) which represent a fraction of the study population. Given the complicated outcomes experienced by some subjects in Dr. Creinin’s study, I am curious about the outcomes of the other subjects in previous case reports who didn’t have positive outcomes (i.e., those who did not have continuing pregnancies).

Catherine Cansino, MD, MPH, is associate clinical professor of obstetrics and gynecology at the University of California, Davis. She was asked to comment on the Creinin et al. article. Dr. Cansino is on the Ob.Gyn. News editorial advisory board.


 

FROM OBSTETRICS & GYNECOLOGY

A study of high-dose progesterone as a mifepristone antagonist to reverse medical abortion has been stopped early because of safety concerns, but the authors say mifepristone antagonization should not be considered impossible.

In Obstetrics & Gynecology, Mitchell D. Creinin, MD, of the University of California, Davis, and coauthors reported the outcomes of a double-blind, placebo-controlled trial investigating the efficacy and safety of high-dose oral progesterone as a mifepristone antagonist. The study intended to enroll more women at 44–63 days of gestation who were planning surgical abortion, but stopped enrolling after 12 patients because of hemorrhage concerns.

Women were given a 200-mg dose of oral mifepristone, then randomized to either 200 mg oral progesterone or placebo 24 hours later, taken twice daily for 3 days then once daily until their planned surgical abortion 14-16 days after enrollment.

The approved method of medical abortion in the United States involves a combination of mifepristone followed by the prostaglandin analogue misoprostol 24-48 hours later, a combination designed to improve efficacy of the treatment.

There have been reports of some patients changing their minds in between taking the mifepristone and the misoprostol. The fact that mifepristone binds strongly to the progesterone receptor has led to the idea that its action could be reversed with high-dose progesterone as an antagonist.

In this study, three women – two in the placebo group and one in the progesterone group – experienced severe bleeding requiring ambulance transport to the emergency department 2-3 days after taking the mifepristone.

The study found that four of the six patients in the progesterone group, and two of the six patients in the placebo group had continuing pregnancies at 2 weeks.

There were two patients – one in each group – who did not complete the study. One in the placebo group left after taking the mifepristone because of anxiety about bleeding, and had a suction aspiration. The second women completed two of the four doses of progesterone, then requested a suction aspiration.

Dr. Creinin and coauthors wrote that while the study ended early, they found that there were no significant differences in the side effects experienced by patients treated with progesterone, compared with those on placebo – apart from a worsening of some pregnancy symptoms such as vomiting and tiredness.

However, patients should be told of the risk of using mifepristone for medical abortion without using misoprostol, they said, as this was associated with severe hemorrhage even with progesterone treatment.

“Because of the potential dangers for patients who opt not to use misoprostol after mifepristone ingestion, any mifepristone antagonization treatment must be considered experimental,” Dr. Creinin and associates wrote.

The Society of Family Planning Research Fund supported the study. One author declared a consultancy with a laboratory providing medical consultation for clinicians regarding mifepristone, and a second author was an employee of Planned Parenthood. No other conflicts of interest were declared.

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