Analysis Maternity and Birthing

What We Know About Three-Parent In Vitro Fertilization

Jessica Cussins

While there is much enthusiasm surrounding experimental new techniques that aim to help women with severely mutated mitochondrial DNA to have a child that would not inherit the disorders that can be caused by those mutations, the verdict is still out on the procedures. And it doesn't look good.

The Food and Drug Administration (FDA) held a public meeting in late February to consider experimental new techniques that would modify human eggs or embryos in an attempt to allow women with severely mutated mitochondrial DNA to have a child that would not inherit the disorders that can be caused by those mutations. The meeting also considered the use of similar techniques for cases of infertility.

The numerous concerns raised during the two-day meeting made it clear that there are still gaping holes in the data and countless issues to work through. But a strange thing happened: Many people from across the political and professional spectrum unexpectedly found common ground. Apparently most people can agree that anyone who hopes to wield that kind of power carries the burden of proof that their technique works, that it would be safe, and that there are no better alternatives.

As of right now, the case for these new technologies does not look very strong.

The procedures, of which there are a couple variations, have been called everything from “mitochondrial manipulation” to “three-parent IVF (in vitro fertilization).” The techniques would remove the nucleus from an egg or embryo of a woman who wants a child and put it into a donated egg or embryo that has had its nucleus removed. Any resulting child would inherit nuclear DNA from their intended mother and mitochondrial DNA from a donor, resulting in the biological first of a child with genetic material from three people. While mitochondria contain only a tiny fraction of a person’s genes, each cell contains hundreds or thousands of copies, and they seem to have an outsized impact on cellular health. The broader effects of this crude DNA mix-and-match are largely unknown.

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I, too, was created in a petri dish. I was an IVF baby. It’s a strange thing to know that my existence is thanks to a technology that, although now widely accepted, some find abhorrent. But IVF is a much less invasive and radical procedure than these egg or embryo manipulations, which would modify every cell of the children born as a result, and would be passed down to future generations. So, back to that burden of proof.

Do the Techniques Work?

Shoukhrat Mitalipov’s lab at Oregon Health and Science University has used its technique on non-human primates, leading to the birth of five rhesus macaques. Though apparently healthy, quantitative data on their comparative health have not been released. And the limitations are obvious: Five is an extremely small sample size, the macaques are still young, and no future generations have been studied.

Both Oregon and Newcastle University researchers have also released papers detailing the use of their respective techniques on human zygotes and embryos. However, both teams note increased abnormalities caused by their manipulations. Furthermore, the briefing document released by the FDA acknowledged that none of the data can be seen as traditional proof-of-concept studies since they were not carried out on eggs or embryos with abnormal mitochondria. The document states, “It is not clear whether these data provide any support for the potential effectiveness of these methods in humans.”

A seemingly forgotten fact by the media is that only about 15 percent of mitochondrial diseases are even caused by mitochondrial DNA. In other words, these techniques would not help 85 percent of the women with mitochondrial diseases. The additional facts that there are hundreds of different mitochondrial diseases, that the mutability of mitochondrial DNA and the variability of mutation-load between cells is widespread and only vaguely understood, and that misdiagnosis of people suffering from mitochondrial diseases is rampant, will make any preclinical trials or eventual usage extremely challenging.

Although there are some studies to suggest female infertility could be linked to a decline in quality and quantity of mitochondria in a woman’s eggs, there is extremely limited data on the efficacy or safety of the use of these techniques for infertile women, and they were widely dismissed at the meeting.

Are the Techniques Safe?

There are risks for the women involved. Large-scale egg extraction requires hormone injections and surgery, which carry short- and long-term risks. For women with mitochondrial diseases, pregnancy also poses a number of serious health risks.

There are known and unknown risks for any resulting children. According to the FDA briefing document, some of the known risks include damage caused to the egg or embryo from the manipulations, nuclear-mitochondrial incompatibility, epigenetic modification of nuclear DNA, and the impact of the chemicals and drugs used at various points throughout the procedure. Problems from any of these issues could quite conceivably show up at any point during embryonic or fetal development, throughout the child’s life, or in future generations. Numerous scientistsbioethicists, and public-health advocates have voiced their grave concern.

The Associated Press reported that it could take decades to understand the safety of these techniques.

Are There Better Alternatives?

For women with mitochondrial diseases who want to have a healthy child, adoption or IVF with the use of a donor’s egg are available options.

For women who want to have a healthy genetically related child, preimplantation genetic diagnosis (PGD) is a promising alternative. PGD is the genetic testing of IVF embryos; it can determine the mutation load of each embryo so that only one with a harmless level of mutations is implanted. A number of studies have shown the promise of PGD in helping women with mitochondrial disease have unaffected children. The only time this would not be an option is if 100 percent of a woman’s mitochondrial DNA is mutated. However in such cases, that woman is likely to be suffering from debilitating illness and the feasibility of her carrying a successful pregnancy could be thrown into question.

So, Why All the Enthusiasm?

Any technology that purports to save lives is bound to garner enthusiasm. There has been a lot of positive hype. Of course, this technology wouldn’t save lives. As Jeffrey Kahn of Johns Hopkins University told Science, “We’re not treating humans. We’re creating humans. There’s not a model for that.”

The creation of genetically manipulated babies would be a huge step for humanity to take. Legally, biologically, and philosophically it would mean crossing into a realm of human experimentation that has been carefully avoided and prohibited in dozens of countries.

The UK government has been considering carving out an exception to their law that prohibits inheritable human genetic modification in order to allow these techniques to move forward. It has just started a three-month open consultation that invites public comment on draft guidance that would regulate the technology. Though the government has decided to undertake this step, it is still uncertain that these techniques will be approved in the UK. After the consultation, the government will ask for an updated assessment on the safety and efficacy of these techniques prior to submitting final regulations for a vote in Parliament.

But, the data itself suggest that the techniques are ineffective, pose serious risks to women and children, and that there are better alternatives out there. This is much of what was discussed at the FDA meeting, and hopefully these critical points will also be brought to the forefront of the UK consultation.

The media attention surrounding these controversial modification techniques has certainly increased public awareness of mitochondrial diseases, and that’s a good thing. Perhaps it’s time to move on from the experimental genetic modification of babies and focus on treatments for people suffering from mitochondrial diseases right now.

Commentary Abortion

A Fact-Based Guide to Resisting Anti-Choice Propaganda in the Wake of the Attack on Planned Parenthood

Andrea Grimes

The phrases being thrown around by conservative legislators and organizations aren't medical terms. They're intentionally deceptive bits of propaganda, and they create an anti-choice political frame for conversations about abortion care that are not rooted in sound science and medicine.

See more of our coverage on the misleading Center for Medical Progress video here.

After the release of a deliberately misleading cut of a video targeting Planned Parenthood for its policies regarding fetal tissue donation, the Texas Attorney General said his office is investigating Planned Parenthood for the “sale of baby body parts.” A number of other states, as well as federal lawmakers, have pledged to do the same thing for these “babies.” The Pro-Life Students Association told its members that Planned Parenthood was selling “the body parts of aborted babies.” A Personhood USA email talked about “preborn human beings.”

These aren’t medical terms. They’re intentionally deceptive bits of propaganda, and they create an anti-choice political frame for conversations about abortion care that are not rooted in sound science and medicine.

But oftentimes, even people who care deeply about reproductive rights aren’t sure how to talk about abortion in the most accurate way. Rewire talked to OB-GYNs and abortion providers—you know, actual doctors!—to compile a list of phrases and terms you’ll often hear during conversations about abortion care, their definitions, and their scientifically correct usage…if, in fact, there is a scientifically correct usage.

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Last menstrual period, LMP: For accuracy’s sake, doctors generally measure pregnancies in weeks, rather than months, and LMP is the measure by which the vast majority of medical professionals calculate the weekly development of an embryo or fetus. It is calculated from the first day of the pregnant person’s last menstrual period. In the first trimester, many doctors use both LMP and an ultrasound to date a pregnancy. However, ultrasounds become less reliable for dating purposes as a pregnancy develops, said one doctor, “because of variations in fetal growth rates as well as margin of error of the technology.” So LMP gives doctors a good overall idea of the length of the pregnancy, and ultrasounds help them monitor fetal development.

Fertilization: The process during which an egg cell (“oocyte,” the thing that ovaries produce) unites with sperm (the thing that testicles produce), to create a zygote, the earliest stage of reproductive development.

Conception: A “metaphysical” term rather than a medical term, which “centers the zygote as a being,” according to an abortion provider who talked to Rewire.

Beginning of Pregnancy: When a fertilized egg successfully implants in the uterine wall. (Or, in cases of ectopic pregnancies, which are unsustainable and life-threatening to the pregnant person, when the fertilized egg implants elsewhere.)

Gestational age: This is a deliberately misleading term (sometimes called “post-fertilization age) that is not widely accepted in scientific use and misapplies the concept of “age” to an embryo or fetus in order to imbue it with the kind of “age” we might think of a child, teenager, or grown adult having. Doctors and other medical professionals, when discussing pregnancy, are not concerned with “age” but with the duration of a pregnancy (in weeks) and the development of that pregnancy. It is generally not possible to reliably pin down the moment of fertilization, so doctors don’t try—they stick with LMP and ultrasounds.

Embryo: The stage of development, in humans, up to nine weeks’ LMP.

Fetus: The stage of development from 10 weeks after LMP until birth.

Products of conception: A medical term to describe the embryonic or fetal contents of a uterus and attendant tissues. “Products of conception isn’t a euphemism,” one abortion provider told Rewire. “It’s an actual proper term [which] encompasses fetus, umbilical cord, membranes, placenta, etc.” If products of conception are present in a uterus, it signals that a pregnancy is not ectopic, wherein a fertilized egg implants somewhere other than a uterus.

Medical, or medication, abortion: An abortion using pharmaceuticals. Most medical abortions are prescribed using a combination of mifepristone (also called Mifeprex or RU-486), which blocks the hormone progesterone (which a body needs in order to continue a pregnancy) and misoprostol (also called Cytotec), which induces contractions.

Emergency contraception: Also known as the “morning-after pill,” it is not the same thing, repeat, NOT the same thing, as a medical abortion. This medication, which can be taken up to a few days after unprotected sex—with certain limitations depending on pharmaceutical content and patient characteristics—prevents, delays, or blocks ovulation, preventing fertilization (without which there can be no fertilized egg and no pregnancy).

Dilation and curettage (D and C): Falls under the category of “surgical abortion,” is also known as an “aspiration” abortion, and is done up to about 13 weeks’ LMP. It’s a medical procedure which requires less dilation than a D and E—”It’s always safer not to enter the uterus with forceps if you don’t need to,” said one provider we spoke to—and uses a suction method to remove products of conception. Why curettage, then? Because older providers were trained to do a sharp curettage, or scraping, after suction, but abortion providers who have been trained more recently tend not to do so. The “c” part of “D and C” stays in because  the suction cannula is sometimes called a “suction curette.”

Dilation and evacuation (D and E): Falls under the category of “surgical abortion.” It’s a medical procedure which involves dilating the cervix (think 1.5 to 2.5 centimeters, as opposed to the 10 centimeters required for a full-term delivery) and a doctor entering the uterus with forceps, usually after about 14 weeks’ LMP depending on fetal development. Forceps are needed to grasp and remove the products of conception. Before the D and E procedure was developed, pregnant people would’ve had to have labor inductions in a hospital setting to facilitate the removal of fetal tissue. D and E procedures, widely misunderstood by anti-choice lawmakers, are recent targets for unnecessarily intrusive legislation that puts pregnant people at risk and prevents doctors from performing the safest possible procedures.

Partial-birth abortion: Not a thing. Well, it’s a string of words put together to make a phrase, so it’s a thing in the sense that a phrase is a noun, but medically, it has no meaning whatsoever. According to one abortion provider, it’s “not a distinction we make.” Instead, abortion providers are concerned with removing the products of conception safely. “A more intact removal, if you have adequate dilation, is safer for the patient,” said the provider, because the doctor makes fewer passes into the uterus. But it’s not something doctors can or do plan for: “You don’t deliberately set out to do an intact extraction, and sometimes you do one by accident.”

Induced abortion: When a pregnancy is ended using medication or surgical abortion care.

Self-induced abortion: When a pregnant person ends their pregnancy outside of a clinical setting.

Spontaneous abortion: A miscarriage.

Stillbirth: The spontaneous loss of a pregnancy (a miscarriage) that has developed past 20 weeks.

Viability: Many laypeople imagine the point of “viability” to mean the threshold at which a fetus is capable of surviving outside the uterus, but that threshold is different for every pregnancy, and greatly dependent on available medical care and existing technology. Generally speaking, medical professionals believe viability begins around 24 weeks’ LMP, and they take into account the likelihood not only of survival, but of disability and quality of life, when weighing potential fetal viability.

Neonate: An infant younger than four weeks old.

Baby: Not a medical term, but nevertheless a word that obstetricians and gynecologists do sometimes use when talking with patients, depending on their patient’s condition, situation, and personal preferences—not as an across-the-board replacement for “zygote,” “embryo,” or “fetus” in order to manipulate their patients’ emotions. Dr. Leah N. Torres, a Utah-based OB-GYN with a focus and training in family planning and reproductive health, told Rewire, “I change my language depending on the patient I’m caring for and their individual situation.” For people who might be losing desired pregnancies, said Torres, “that fetus has a high school diploma and is getting married once the urine test is positive”—in other words, that’s what some patients have imagined for the future—so she’s comfortable using “baby.” For someone having an abortion, Torres said she might be more likely to use “pregnancy” or “fetus.” But overall, she said, she prefers “to use the catch-all term ‘pregnancy’ which is medical and neutral and applies to all stages of the pregnancy.”

Person: A born human being who is not currently the occupant of a uterus and not therefore dependent on a human uterus for their continued development. I’ll let Torres take the rest of this one: “A person is a social or philosophical construct that, if applied to fetuses, will necessarily revoke the personhood of the pregnant person due to the ‘power’ imbalance and physical dependence of one upon the other. Miscarriage as involuntary manslaughter, if you will.”

Analysis Human Rights

Woman in El Salvador Acquitted of Homicide Charges for Pregnancy Complications

Kathy Bougher

Carmelina Pérez, a Honduran woman living in El Salvador, was sentenced to 30 years in prison in July 2014 after suffering what appeared to be a miscarriage. But last week, she was acquitted of all charges, setting a possible new precedent in the fight for reproductive justice in El Salvador.

Read more of our coverage on the campaign for Las 17, the 17 Salvadoran women imprisoned on abortion-related charges, here.

Carmelina Pérez, a Honduran woman living in El Salvador, was convicted of aggravated homicide and sentenced to 30 years in prison in July 2014 after suffering what appeared to be a miscarriage in the home where she was employed as a domestic worker. Pérez is not one of “Las 17,” the group of women imprisoned on abortion-related charges and for whom the La Agrupación Ciudadana por la Despenalización del Aborto (Citizen Group for the Decriminalization of Abortion) requested pardons from the Salvadoran government, because her case had not yet gone to trial at the time of their requests. Her story mirrors theirs, however: She, too, had her obstetrical emergency criminalized.

But last week, she was acquitted of all charges after 16 months in prison, setting a possible new precedent in the fight for reproductive justice in El Salvador.

In addition to creating a joyous victory for Pérez, now 21 years old, her trial provides an opportunity to expose and analyze in detail the medical and legal injustices that women frequently face in El Salvador.

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Pérez had left her isolated community in Honduras to find employment as a live-in domestic worker with a family in rural eastern El Salvador. When she became pregnant, she was afraid to tell her employers for fear of losing the job, her only means of supporting the toddler son and elderly parents she’d left in Honduras. According to Pérez, she went into labor and gave birth alone on January 1, 2014, to a fetus that did not survive.

She hemorrhaged heavily, and eventually her employer took her to the local public hospital, without realizing that she had just given birth. Under questioning from the physician who treated her, Pérez acknowledged that she’d had a miscarriage. That physician accused her of abortion and notified police, who took her into custody. On July 3, 2014, she was convicted of aggravated homicide and sentenced to 30 years in prison.

In an on-the-ground interview with Rewire after the trial, Agrupación attorney Dennis Muñoz, who represented Pérez along with Daniela Ramos, described that first trial as riddled with “prosecutorial flaws” and heavily “influenced by prejudices” against women. On July 30, Muñoz and Ramos filed an appeal.

Doctor-Patient Confidentiality

Salvadoran law mandates doctor-patient confidentiality, but it also requires doctors to report suspected abortions or other crimes. However, another clause addresses that contradiction when it says that the duty to report crimes does not apply if the information is gained through a confidential relationship.

In what the attorneys called a “precedent-setting” decision, the appeals court ruled on September 22, 2014 that the physician who treated Pérez in the public hospital where she sought emergency treatment had violated doctor-patient confidentiality by testifying against Pérez in court and revealing information gained only through that protected relationship. Even though Muñoz had objected to the doctor’s testimony during the first trial, citing the violation of professional confidentiality, that judge had allowed the doctor to testify.

Significantly, the appeals court ruling stated that the confidentiality violation was automatic grounds for annulment of the trial and the conviction. It also called for a new trial to take place, where the fight over doctor-patient confidentiality continued to play out. To the surprise of the defense attorneys, the same prosecutor attempted to have the same physician testify again—a clear violation of the appeals court’s order.

In a Skype interview with Rewire after the second trial, Muñoz said that when he objected to the doctor’s testimony and referred to the appeals court decision, the prosecutor insisted that she needed the testimony from the physician to make her case.

Attorney Jose Santos Guardado, who joined Muñoz and Ramos at the second trial, noted during the Skype interview that when the judge asked the physician to explain her understanding of doctor-patient confidentiality, she replied that it was her duty to testify because she was an employee in a public hospital, and thus it was her responsibility to help the government detect and pursue crimes. Therefore, the physician felt that doctor-patient confidentiality did not apply in the public hospital. This understanding, however, is not consistent with the law.

According to the three attorneys, the judge explained to the physician that she would be violating the law if she testified. He ordered her to leave the courtroom. Muñoz and Ramos note that the doctor and the prosecutor may have exposed themselves to potential criminal charges stemming from the doctor’s testimony at the first trial, an issue the Agrupación may explore. At the least, the lawyers hope the judge’s actions will send a strong message to other prosecutors and physicians.

Although perhaps not her intention, the doctor’s comment also illustrates a reality the Agrupación has observed widely—that poor women are often discriminated against in public hospitals. The Agrupación noted in its 2012 research findings, Del Hospital a la Cárcel (From the Hospital to the Jail), that of all the cases its members found in the country between 2000 and 2011, not a single woman had been reported to police with abortion-related charges by medical personnel in a private clinic or hospital. All the reports had come from public hospitals, the only health care available for most poor women. Although it is possible that women with obstetrical emergencies that are seen as suspected abortions don’t arrive at private hospitals, the Agrupación noted in the report, it appears more likely that the private hospitals simply don’t report their patients to the police. This results in discrimination against women who cannot afford private hospitals.

In the Las 17 cases, records demonstrate that public hospital physicians were frequently the ones who made the initial police report. They were also often asked to testify against their patients—thus calling doctor-patient confidentiality into question. However, the issue has never received judicial attention until now. Ramos and Muñoz believe the point will be important as the Agrupación continues to fight for the freedom of Las 17 and others who are still imprisoned.

Proof of a Committed Crime

The appeals court also addressed another major legal issue that Salvadoran courts have frequently ignored: The prosecution must prove the accused person took action to commit a crime, and the judge must base a conviction on this evidence, not on supposition or speculation. In a legal system that has never before been successfully challenged on its fundamentalist-influenced thinking about traditional roles of women and mothers, this was a victory.

A significant example of how this played out arose when the appeals court noted the judge’s decision to convict in the first trial was based on the argument that since Pérez was in the same room with the baby and the DNA evidence proved that she was its mother, that was sufficient reason to convict her. The first judge’s decision, ruled the appeals court, also discounted any alternative explanations for how the newborn suffered the cranial injuries that were demonstrated by the autopsy. At the first trial, the prosecutor and the judge alleged, without presenting any evidence, that Pérez had struck or thrown the live baby against a hard surface. That formed a significant part of the judge’s rationale for convicting her.

In its appeal request the Agrupación challenged this supposition and suggested the possibility that the injuries could have resulted from the birth itself: that the baby hit the floor when it left its mother’s body.

The appeals court recognized the validity of this argument, and found that the prosecution in the first trial did not fulfill its responsibility to present evidence to support its allegations, leaving doubt as to how the injuries occurred.

At the second trial, the prosecutor made the same unfounded allegation, and the Agrupación challenged it again. The difference was that the second judge made a decision based on scientific evidence rather than what the appeals court had termed “emotional inferences.” The judge agreed that cranial trauma appeared to be the baby’s cause of death. However, he ruled that the prosecution failed to provide evidence of how that cranial trauma occurred or evidence of any actions taken by Pérez to cause that trauma.

Salvadoran law says that when there are doubts in a case, the benefit of the doubt goes to the accused. Muñoz said Pérez’s trial was a “rare example” of when this right has been respected in these circumstances.

As the three attorneys acknowledged, the fact that the second judge was willing to allow lawyers to fully present their arguments (other judges have cut off testimony), listened carefully, and made decisions according to the law was what gave Pérez her victory.

About Las 17, Guardado emphasized, “If the other 17 women had had fair trials, they wouldn’t be in prison now.” Of course, part of a fair trial is a competent, adequate legal defense, which has not always been provided, the Agrupación has argued, by other women’s public defenders. By contrast, the Agrupación attorneys represented Pérez at her original trial.

Ramos agreed that if the judge or the quality of the legal defense had been different, Pérez could well be in prison now, too.

In their defense of Pérez, Guardado told Rewire, “We were adamant that it is not illegal to be young, vulnerable, poor, and frightened when facing a pregnancy under precarious circumstances, nor is it illegal to hide a pregnancy or go without prenatal care. It’s a reflection on the socio-economic conditions of poor women in our country, not on their guilt.”

What Happens Now?

Pérez’s victory contributes to the momentum the Agrupación has built recently in its fight for justice. In January the government granted a pardon for one of Las 17, an historic event. Then, this spring, the Inter-American Commission on Human Rights (IACHR) agreed to hear two potentially game-changing cases—that of Beatriz, a woman denied a life-saving abortion by the Supreme Court, and Manuela, a woman serving a 30-year sentence for aggravated homicide who died of under-treated cancer while in prison. The government must provide the IACHR with explanations and remedies for those events by late June. If the IACHR rules against the Salvadoran government, it could demand “measures to prevent repetition,” which could mean significant changes in laws and in public hospital procedures.

On April 22, Amnesty International brought petitions with more than 300,000 signatures in favor of changing abortion laws to El Salvador. Amnesty and the Agrupación presented the petitions to President Salvador Sanchez-Ceren, the Supreme Court, and the leaders of the Legislative Assembly as part of the campaign to initiate a national dialogue on the question of abortion.

Of course, the politically and economically powerful Salvadoran right-wing forces who oppose the work of the Agrupación continue their campaigns, too, so the struggle is still uphill.

Pérez remains in El Salvador awaiting the final bureaucratic steps in her case, anxious to leave the country and return to her young son and her mother in Honduras. She told Rewire in a telephone interview that she is “happy and grateful” to be out of prison.

Under Salvadoran law, the prosecution can also appeal Pérez’s acquittal and request yet another trial. If that happens, Ramos said, “then we just keep fighting.”