OB/GYN Ethics 201

In OB/GYN Ethics 101, I covered the basics for medical students and residents rotating through OB/GYN settings, and a little for OB/GYN residents. This post is about three sorts of hard cases: induction of labor before viability, emergency contraception, and methotrexate.

In OB/GYN 101, I wrote:

Do not induce labor for inevitable abortion, i.e. when fetal death has not occurred

It is true that uncomplicated inevitable abortion should be managed expectantly, especially if there is a question in diagnosis. However, there are situations in which labor can be induced because of the principle of double effect.

Previable chorioamnionitis
If a woman develops chorioamnionitis prior to viability (either spontaneously or because of previable PPROM), the principle of double effect permits induction of labor if chorioamnionitis is clearly present and either is too severe or too remote from delivery for antibiotics to preserve the lives of mother and fetus. Richard White explains:

The early induction of labor...satisfies the four conditions of double effect. First, it can be assumed that the intention of both mother and physician is to evacuate the infected chorion and amnion. Second, in light of the serious infection and its threat to the lives of both mother and fetus, treatment is needed to save the life of the mother; that the mother’s life can only be saved by inducing labor is a proportionate reason to perform the procedure. Third, since the early induction of labor does not target the fetus, but the evacuation of the pathological tissues, the death of the fetus is not a means to achieve the health of the mother. And, fourth, there is no alternate procedure to treat the chorioamnionitis with the promptness required by the situation. (1)

Persistent Eclampsia (or Complicated Pre-eclampsia)

In the case of a previable patient whose seizures and severe-range blood pressures do not respond to magnesium and IV antihypertensives, delivery can be expedited by induction. The same can be true of a mother with worsening complications from previable pre-eclampsia (e.g. renal failure or respiratory distress), or evolving HELLP syndrome. White notes:

The act of inducing labor, in this case, appears to satisfy all the conditions of the principle of double effect. First, the act removes the offending placenta, which is the cause of eclampsia. This action is therapeutic for the mother and is, thus, good. Second, the intention of the physician and the mother are, presumably, directed towards the treatment of eclampsia, not towards the termination of the pregnancy. Third, cure of the condition is not achieved by removing the fetus, but by removing the offending placenta. Fourth, the mother’s life is endangered by the complications of eclampsia, which have manifested; the various threats to the mother’s life that the complications pose are proportionate to the induction’s consequences for the child. Fifth, all other methods of treatment that would not result in the death of the fetus (i.e., expectant management) have been exhausted. (1)

§

In OB/GYN Ethics 101, I said:

Do not advise the use of any hormonal contraceptive (e.g. mirena) in sexually active patients. Period. This is because of their post-fertilization effects.

It is true that patients should not use hormonal contraceptives because when used throughout the cycle, they will inevitable have post-fertilization effects. But when you, a physician, are in control of when those hormonal contraceptives are used, you can use them licitly to avoid the post-fertilization effects.

Emergency Contraception
Emergency contracpetion (EC) has its own post. But here's quick a rundown:

1. Hormonal pills: can be licit. Remember that hormones to prevent pregnancy are not proscribed except to the married, and self-defense is licit, even defending oneself against the effects of an act, such as advancing sperm. A pregnancy test is not enough to exclude the potential post-fertilization effects of emergency contraceptives. The Peoria Protocol lays out how to tell with moral certainty that a woman has not ovulated and that the primary effect of EC is anti-ovulatory. It involves serum progesterone (<1.5 is pre-ovulatory, okay to give EC) and urine LH (negative is pre-ovulatory, okay to give EC). Notice I didn't give units. Do not use cutoffs a blog post to determine management of patients requesting EC. You need a working relationship with your hospital lab and you need to be better acquainted with the Protocol's other reference ranges for progesterone before you can use it.


2. Hormonal IUDs: insertion of a mirena or skyla as EC relies not only on the anti-ovulatory effects of the levonorgestrel, but also on the intrauterine effects, which act after fertilization. Although it may be argued that application of the Peoria Protocol could allow these effects to be avoided, a systemic hormone (to reach the hypothalamus) is more targeted than an IUD (which would also have to be removed if the patient is later sexually active.


3. Paragard: this relies on post-fertilization effects (which is why it works up to five days after the act of intercourse), and cannot be licitly used.


4. Plan B: is levonorgestrel, given in one 1.5mg dose or two 0.75mg doses twelve hours apart. Strangely, we can't seem to figure out whether its main effect is primarily anti-ovulatory or post-fertilization. A recent (2015) review of all the data in the Linacre (2) concluded that "arguments used to justify use of [Plan B] as a non-abortifacient drug carry substantial weaknesses; in addition, the preovulatory administration of LNG-EC does not consistently alter sperm or ova flow and function, yet there is absence of clinical pregnancy in cases where fertilization is likely, which suggests that abortion is a likely mechanism of action. Therefore, the claim that moral certitude exists via LNG-EC’s nonabortifacient action is currently indefensible."


5. Ella: ulipristal is a selective progesterone receptor modulator. It is given in one 30 mg dose. It antagonizes progesterone at its receptors on the endometrium, which mean it only has post-fertilization effects. This is the same mechanism of action as mifepristone (RU486, which is given in doses of 600mg for elective abortions). Although package inserts deny that it is abortifacient, this indicates that a 30mg dose is not suspected to have post-implantation effects. For a Catholic who understands life to begin at sperm-egg fusion, ulipristal is extremely likely to lead to loss of embryonic life.

§

Ectopic Pregnancy
All the above is generally agreed upon. Going forward, I am about to make some people disagree with me. This is because the magisterium has not spoken on this issue and faithful Catholic theologians (who all agree that life should be protected from fertilization to natural end) can legitimately disagree. This disagreement is good and fruitful.

In short: salpingectomy is fine, principle of double effect applies.

Salpingostomy: also fine, principle of double effect applies. (Alert! Not everyone agrees with me, but some of the theologians who thought this was not licit have come to agree. An excellent article by Christopher Kaczor in the Linacre defended this very soundly (3). I am morally certain that this is permissible.)

Methotrexate: has its own post. The same excellent article in the Linacre did not defend this very soundly at all, but I propose a different defense, which takes into account more embryology, more sonography, and more other examples from medicine than I have seen others do.

Like all sinners who want to be faithful Catholics, I submit every word of this post to the judgement of the Church.

---

References not linked:

1. Richard White. "Prenatal Complications." The Linacre Quarterly 2009; 76(3), 304-309. DOI: 10.1179/002436309803889098
2. Chris Kahlenborn, Rebecca Peck and Walter B. Severs. "Mechanism of action of levonorgestrel emergency contraception." The Linacre Quarterly 2015; 82(1), 18-33. DOI: 10.1179/2050854914Y.0000000026
3. Christopher Kaczor. "The Ethics of Ectopic Pregnancy: A Critical Reconsideration of Salpingostomy and Methotrexate." The Linacre Quarterly 2009; 76(3), 265-282. DOI: 10.1179/002436309803889106

Methotrexate

I used to think methotrexate (MTX) was an unacceptable way to treat ectopic pregnancy. Like personal heroes William May and Fr. Tad Pacholcyzk, I saw MTX as a direct attack on fetal cells. MTX was akin to (if not identical to) direct medical abortion.

The question I ask today is: is that true?

Background

MTX inhibits DNA synthesis and has (relatively) selective toxicity to rapidly dividing cells. It appears to select trophoblastic tissue (early placenta) rather than fetal tissue. It is administered for ectopic pregnancies to prevent rupture, which occurs in 0.5% of cases.

MTX can only be given if the mother is hemodynamically stable and if she will be able to follow up with serial hCG measurements. It is considered more strongly if the patient desires future fertility or is a poor surgical candidate. She must have an unruptured ectopic with a gestational sac less than 3.5cm in greatest diameter, there must be no cardiac motion, and the hCG should not exceed 5000-6000 mIU/mL. Further, the following must not be present (these are absolute contraindications):

1. Breastfeeding
2. Immunodeficiency
3. Liver disease (including alcoholism)
4. Blood dyscrasias (e.g. thrombocytopenia)
5. Active pulmonary disease
6. Peptic ulcer disease
7. Renal dysfunction

Double Effect
The fetus always dies in current ways to treat ectopic pregnancy. Thus, any treatment other than expectant management must employ the principle of double effect. The principle of double effect can only apply if:

1. The act in question (or the procedure) must be "good" or "neutral" in its moral quality,
2. The good effect is intended, not the bad,
3. The good and bad effects must occur simultaneously, thus avoiding a situation in which the bad effect becomes a means for achieving the good effect, and
4. There should be a proportionate reason, that is, a sufficiently serious reason, to permit the bad effect.

Can the first criterion of the principle of double effect ever apply to methotrexate? The drug is acting directly on a vital organ of the fetus and as such "“a direct and lethal attack on the body of an unborn child" (1). For many years, this has persuaded Catholic theologians that use of methotrexate is illicit, because the "act in question" is not good or neutral.

Christopher Kaczor attempted to defend MTX in 2009, citing some work by Fr. Albert Moraczewski and others (2). He attempts to argue that most administrations of MTX occur after fetal death*, that MTX might be construed as stopping damage to the tube (a secondary effect, at best), that the trophoblast is not a vital organ of the fetus alone (which I find untenable, since its growth is entirely fetus-driven, even though it makes a barrier between mother and child), and that administration of MTX could be considered not "intentional" destruction of the trophoblast (which I find patently false, as that is the sole reason we're giving it).

I don't think Kaczor knocks down the fundamental point: MTX is the destruction of a vital organ of the fetus. I don't think anyone will be able to knock down this point. It's true.

Ectopia and "Diseased"
MTX destroys a vital organ of the innocent human embryo. Strange (and sad) as it may seem, I don't think that poses a problem.

Ablation or resection of vital organs is at times necessary when such organs are diseased. "Diseased" (like "conception") is not a medical term, and it can be difficult for medical professionals to nail down exactly what ethicists had in mind when the word was chosen for moral teaching. I suggest that "diseased" be taken to mean "not according to nature," or not "always or for the most part" (3). 
Trophoblastic tissue, for the most part, implants in the uterine cavity. I suggest that this means it is "diseased." It's not infected or full of cancer, but "diseased" means more than that. In fact, this early placenta is like a tiny failing heart, because it's not implanted in an area designed for it, with the appropriate architecture and blood supply to support it. 

Not all ectopic tissue requires removal. A benign uterine leiomyoma (fibroid) that causes no symptoms should be left alone. But ectopic trophoblast (as in ectopic pregnancy) can pose a danger to the mother. Moreover, ectopic trophoblasts are not the only ectopic tissue that require ablation or removal. Prolactinomas and other endocrinologically active macroadenomas, undescended testes, ectopia lentis**, and arteriovenous malformations are other examples.

Conclusion
Use of methotrexate is legitimate, because the four criteria of the principle of double effect apply. Most importantly, the use of methotrexate itself is morally good (or at least neutral). Although it is removal of a vital organ, it is not a mutilation, as ectopia represents a true disease state when the misplacement threatens human life (in this case, it threatens the fetus with inevitable death, and the mother with possible death or danger).

---

Notes
* In addition, some will argue that not all products of conception are fetuses, therefore methotrexate is legitimate for "abnormal" pregnancies, such as those without doubling of beta hCG over 48 hours. This argument is shaky. The minimum rise in beta hCG in a normal pregnancy is 35% over 48 hours (99.9% CI) and 4.6% of patients (n=1,249) with an hCG rise of less than that still went on to have a normal pregnancy (4). Even if this were not true, we must be cautious rather than miss one case of viable pregnancy. When we don't know whether the product of conception is a person, we must assume it is in order to protect human life at all stages.

** Ectopia lentis does not always require vitrectomy or lensectomy.

Bibliography

1. Charles Cavagnaro cited in Anderson MA et al. Ectopic pregnancy and Catholic morality. NCBQ; Spring 2011;667-684. Here.
2. Kaczor C. The ethics of ectopic pregnancy. Linacre Quarterly; August 2009;265-282. Here.
3. Aristotle. Physics II:2. Here.
4. Seeber BE et al. Application of redefined human chorionic gonadotropin curves for the diagnosis of women at risk for ectopic pregnancy. Fertil Steril 2006;86:454–459. Here.