Medical Abortion Overview
Mifepristone medical abortion requires the use of two drugs: mifepristone and misoprostol. Mifepristone is an antiprogestin taken orally during the first trimester of pregnancy. It blocks receptors of the hormone progesterone. As a result, the lining of the uterus can no longer sustain the growing embryo. The drug also increases prostaglandin levels and dilates the cervix, facilitating abortion. Misoprostol is a prostaglandin analog that is marketed worldwide in over 60 countries for treatment and prevention of gastric ulcers. It is widely used “off-label” for a number of reproductive health indications.
One tablet of mifepristone is swallowed first, causing the embryo to stop growing. Two days later, the woman takes misoprostol, causing contractions of the uterus and expelling the uterine products. The timing, dose, and route of administration of misoprostol often vary slightly. Studies have shown that these drugs effectively terminate more than 9 out of 10 pregnancies in the early first trimester.
Introduction of Medical Abortion in Developing Countries
Complications of abortion are among the most important causes of maternal death globally. In Africa, it is estimated that there are 22 unsafe abortions per 1,000 women; nearly one-fifth of all maternal deaths in the region are linked to unsafe abortion practices. In many low resource countries with limited access to health care services and few trained surgical abortion providers, medical methods of abortion promise to help reduce maternal morbidity and mortality.
To date, mifepristone has been registered in over 35 countries, but most of these are in the industrialized world. Fewer developing countries have made this drug available in part because of more restrictive abortion laws, the expense of the drug, and reluctance to allow the pill on the market. Even doing clinical testing of the acceptability and feasibility of the use of the drug can be daunting because of unclear regulatory requirements and political controversies. Gynuity works in low resource settings to help support introduction of this promising technology.
Medical Abortion Regimens Improvement
Medical abortion regimens using mifepristone with misoprostol and misoprostol alone are quickly gaining support worldwide as safe and effective alternatives to surgical abortion. However, it is widely believed that the most frequently registered regimen may not be ideal for use in a range of settings. Refinements to the standard regimen of mifepristone and misoprostol promise to increase access to this method while sustaining high safety, efficacy, and acceptability profiles. Each of these refinements also may lower the costs of providing safe abortion services.
Gynuity conducts a significant amount of clinical research with the goal of refining medical abortion regimens in order to increase efficacy and acceptability, and reduce side effects and costs associated with the method.
Decrease in Use of Routine Sonography
Mifepristone medical abortion has been rapidly accepted in the US since its 2000 approval. Yet the technology has not yet been able fully to deliver on its promise to offer American women a new, widely available alternative to surgical abortion for a number of reasons. Among them are the requirement that women come in to a clinic for a minimum of two visits and the tendency to require pre- and post-procedure sonography as part of treatment. These two factors render medical abortion more burdensome and expensive and limit its provision to practitioners who have sonography machines and the skills to use them.
Gynuity has launched a project to lay the groundwork for decreasing the number of clinic visits and the use of sonography in medical abortion. The project involves more than 4,000 women recruited from four clinics providing medical abortion. The study aims to determine if a simplified approach to medical abortion is as successful as current practice of routine sonography at diagnosing ongoing pregnancies. The study also seeks to discover whether or not symptoms, examination, and a low-sensitivity pregnancy test can, without recourse to sonographic data, in most cases adequately determine duration of pregnancy, likelihood of ectopic pregnancy, and presence of ongoing pregnancy or other post-abortion complications.
Misoprostol Alone Regimens for Early Termination of Pregnancy
A wealth of evidence in the scientific literature indicates that misoprostol alone can be used safely and effectively for early pregnancy termination. However, no formal drug development strategy or authoritative advice on appropriate regimens existed for use of misoprostol for this indication.
To address the need for clinical guidelines for early abortion with misoprostol alone, Gynuity and the Reproductive Health Technologies Project convened a small expert meeting in July 2003 to review the medical literature, discuss the clinical aspects of various regimens, and agree on clinical advice for use of misoprostol for this indication. That advice can be found in a brochure entitled “Instructions for Use: Abortion Induction with Misoprostol in Pregnancies through 9 Weeks LMP.”
Gynuity also conducts clinical research to help refine misoprostol alone regimens for early pregnancy termination with the goal of increasing efficacy and acceptability, and reducing side effects and costs associated with provision of this method.
Pain Management in Early Medical Abortion
Although pain is a principal reason that women give for dissatisfaction with medical abortion, evidence about methods to control pain in this procedure is surprisingly scant. Because this pain can have a rapid progression, initiating analgesia before the onset of pain may produce a more satisfactory result than waiting until the pain occurs.
Gynuity is conducting a randomized trial to compare two regimens of ibuprofen: a treatment regimen consisting of ibuprofen as needed for pain, and a prophylactic, “around-the-clock” regimen that is starting 1 hour before the misoprostol dose, then four times a day for at least 2 days regardless of pain. The study will include 250 women undergoing first trimester abortion at two large abortion facilities, Family Planning Associates Medical Group (Chicago, IL) and Planned Parenthood of New York City. The study outcomes will include amount of pain experienced, total amount of ibuprofen taken, use of other analgesics, vaginal bleeding, adverse events, successful completion of abortion, and overall satisfaction with the abortion procedure.
Multi-Level Pregnancy Test
The multi-level pregnancy test (MLPT) is a five-bracketed immunochromatographic assay panel that operates as both a high sensitivity and a low sensitivity measure of hCG, the pregnancy hormone. It provides readings of five thresholds: at least 25, at least 100, at least 500, at least 2000, and at least 10,000 mIU/mL. The test offers a technical improvement over other urine pregnancy tests in that it provides information about the trend in hCG levels. The test can be performed and read in under 20 minutes by women at home or by clinicians in a medical setting.
The MLPT can be used to monitor trends in hCG levels over time, both increasing and decreasing levels. In normal pregnancies, hCG levels double every 48 – 72 hours, peaking at 8 – 11 weeks of pregnancy and then declining for the remainder of the pregnancy. Following medical abortion, a decrease in hCG level can be used to confirm a successful abortion. For women undergoing fertility treatment, the test could be used to monitor hCG levels and document an increase in hCG.
MLPT for medical abortion follow-up
Common medical abortion practice includes clinic-based follow-up with assessment, often including transvaginal ultrasound, to determine each woman’s abortion status. This follow-up visit can be costly and time consuming for both the health care system and women. As medical abortion becomes more widely used, many women simply do not return to the clinic to receive a clinician’s confirmation of complete abortion. Providing women with a safe, effective and affordable at-home diagnostic tool to confirm if a pregnancy is ongoing after administration of mifepristone and misoprostol could reduce costs and simplify the procedure by limiting the number of clinic visits, costly exams and waiting time. Ideally, a woman could receive abortion drugs, a pregnancy test (MLPT), and counseling on how to manage her abortion at home at her initial clinic visit. She would also be given guidelines for following-up with the clinic if needed. With these tools, the majority of women could manage their abortion follow-up at home.
Gynuity has been exploring the efficacy and acceptability of using the MLPT at home 1-2 weeks following medical abortion in the US, Vietnam, and Moldova & Uzbekistan. In these studies, the MLPT was used at the time the woman took the mifepristone (to establish a baseline) and then on the morning of standard medical abortion follow-up, which was one week after mifepristone in the U.S. and two weeks after mifepristone in the other three countries. The MLPT was highly successful in identifying ongoing pregnancy at one and two weeks post-mifepristone. Of the 2,505 uses and 32 ongoing pregnancies, only 1 ongoing pregnancy was reported as not identified at home with the test, and that woman later self-identified. Approximately 90% of all women felt that the test was easy or very easy to use.
If the multi-level pregnancy test could be successfully used even earlier post treatment, this would constitute an important service delivery improvement: it would shorten the duration of the procedure by 3– 10 days. A shorter procedure is generally preferable to women, and earlier follow-up would likely help reduce lost-to-follow up rates in some settings. One current study explores whether the MLPT would be able to document a decline in hCG level sufficiently to provide similar sensitivity and sensitivity to a 7-day follow-up. The results could lay the groundwork for streamlined medical abortion care worldwide by shortening the duration of the procedure and reducing the number of additional clinic visits required for each medical abortion client.
MLPT for use in fertility treatment
In both high and low-income settings, assisted fertility care entails numerous clinic visits, lab tests and ultrasounds, often at high cost to the woman. Standard monitoring protocols after embryo transfer or (intrauterine insemination (IUI) include continuous sequential pregnancy tests, serum hCG analyses and ultrasound – all done on a regular (at times weekly) basis in a clinic setting. The MLPT could be incorporated into existing models of care for use as an outpatient tool to help women: 1) ascertain initial presence of the pregnancy hormone hCG, and 2) monitor hCG level to confirm that it is increasing appropriately in the early weeks after embryo transfer or IUI. Monitoring with a a MLPT promises to be less costly for the woman and health care system. Also, it may allow the woman to know earlier if she has a growing pregnancy as serial testing at home could begin earlier and be more frequent than current clinic-based monitoring protocols. Gynuity is conducting pilot studies to examine the feasibility and acceptability of using a MLPT at home to help monitor pregnancy progress during assisted fertility treatment.
Providing medical abortion using telemedicine
Access to abortion in the U.S. is becoming increasingly limited. Since 2011, at least 162 providers have closed, while only 21 have opened. At least 4 states have only 1 abortion provider, and it is not uncommon for some women to travel 50 or more miles to reach the nearest facility. The time, money, lost wages, and childcare arrangements involved in accessing this basic reproductive right can be a substantial hardship for many women.
One way to reduce these barriers would be to enable women to obtain abortions without going in person to an abortion provider – that is, by telemedicine. Telemedicine is the remote delivery of health care services and clinical information using a variety of telecommunications including phone, video, and the internet. Use of telemedicine has grown rapidly and is now a multi-billion-dollar industry.
Gynuity is conducting a pilot study of a telemedicine abortion service called TelAbortion. We are looking at the safety and feasibility of operating this model of service, and its acceptability to patients and providers. We will enroll 50 women in Hawaii, New York, Oregon and Washington State. Eligible patients obtain standard pre-abortion tests at facilities close to them. The abortion providers in our study review the test results, and if everything looks fine, mail the abortion pills to the patient. The patient has post-abortion tests also at facilities close to her, and a follow-up consultation with the provider.
Read press coverage about the TelAbortion project here:
The New York Times, A Study Tests the Safety of Women Using Abortion Pills Sent by Mail, November 10, 2016.
The Guardian, Abortion without the clinic on offer with revolutionary new US program, March 31, 2016.
Tonic, How the Post Office Could Solve Abortion Access, November 23, 2016.