Who to Believe - Hobby Lobby, FDA, Someone Else???

Unless you have been living under a rock, you have heard many voices expressing opinions about the recent Supreme Court decision allowing Hobby Lobby to not cover 4 contraceptives of the 20 required under the Affordable Care Act.  I’m a reproductive physiologist by training and did my Master’s thesis research on estrous cycle synchronization.  Amazingly, I chose this path because there is little else in the world that is more interesting and cool to me than hormonal control of reproduction. 

It seems there is a lot of information being thrown around without citation, so how do you know what is REALLY going on?  Hobby Lobby objects to 4 contraceptives – Ella, Plan-B, Mirena (hormonal IUD), and Paragard (copper IUD) – on the basis that they may end a human life.  However, there are many voices that are claiming this is not the case.  The below quote is one such voice.

“Well, you might ask, based upon some of the charges being made, aren't the contraceptive methods being funded through the Affordable Care Act, abortifacients? Not if you believe medical science.  In the words of Jeffrey F. Peipert, M.D., Ph.D., the Robert J. Terry Professor of Obstetrics & Gynecology at Washington University School of Medicine, "these contraceptive methods work by preventing pregnancy (fertilization) from occurring in the first place. For instance, the intrauterine device works primarily by preventing fertilization. Plan B (or the progestin-containing, morning-after pill), along with Ella (ulipristal acetate), delay the release of a woman's egg from her ovary. The egg does not get fertilized, which means the woman does not become pregnant."” (Blog 2)

There are really 2 questions at play in this discussion.  First, how do you define ‘pregnancy’ and second, do the 4 contraceptives in question have the potential to prevent normal development of a zygote/ fertilized egg.

Most people think the first question I have presented is pretty straightforward.  However, ‘pregnancy’ is not the same as ‘fertilization’.  If you can think back to previous biology courses, ‘fertilization’ is the moment when the egg and sperm fuse and form a new diploid cell.  This occurs in the oviduct/ Fallopian tube of the mother.  It is days before the embryo reaches the uterus where it will implant for nourishment for the next 8-ish months.  For many, a substance is not an abortifacient unless it terminates a pregnancy.  Therefore, a substance does not end a pregnancy if it only prevents the embryo from implanting in the uterus.  For additional information about the definition of pregnancy, you should view the following website -  http://thefederalist.com/2014/05/19/the-washington-post-is-super-confused-about-where-babies-come-from/

As one who holds to the view that human life begins at the moment of fertilization, it is important to continue to answer the second question I have posed above – do any of the 4 contraceptives in question have the potential to prevent normal development of a zygote/ fertilized egg.  Might these substances have the ability to prevent an embryo from implanting in the wall of the mother’s uterus?

As a scientist, I answer these questions by viewing journal articles in the primary literature.  Here is a summary of the information I have located by doing such a search in the past week.

ELLA

“The principal effect of ulipristal acetate is to inhibit or delay ovulation, but the mechanism by which this occurs has not be fully clarified….Results of animal studies suggest that ulipristal acetate may have a direct inhibitory effect on follicular rupture.” (McKeage & Croxtall 2011)  This same review article also mentions a minimal effect on the endometrium and an alteration of ‘progesterone-dependent markers of implantation’ within the endometrial epithelium.

MIRENA

“Intrauterine devices (IUD) exert contraceptive action by interfering with sperm transport, ovum development, fertilization, and implantation.” (Mandelin et al. 1997)

I did another search for the mechanism of action of Mirena several years ago and found no studies that showed a post-fertilization effect.  Most studies concluded the main mechanism of action was to interfere with fertilization for both the sperm and ova.  Sperm are not able to fertilize an egg until that are ‘capacitated’ (this process is beyond the scope of this blog) – Mirena’s action prevented this process from occurring.  It also showed an action of ‘zona blocking’ – making the outer covering of the zygote impenetrable to sperm – again, no fertilization.  Unfortunately, I was unable to locate these studies in my search of the literature.  I am guessing this was due to having access to different journal databases.

PARAGARD

“The copper IUD is nonhormonal and continuously releases copper into the intrauterine cavity.  It prevents pregnancy by interfering with fertilization and preventing implantation.” (Bosworth et al. 2014)  “The modern banded copper IUDs are highly effective. The copper IUD acts primarily by preventing fertilisation, the copper ion being toxic to the sperm. Implantation is also impeded, enabling the device to be effective when used for post-coital contraception (Standford and Mikolajczyk 2002, Bhathena & Guillebaud 2008).

PLAN-B

“Levonorgestrel (LNG) works in several different mechanisms depending on the cycle day of unprotected intercourse and the day on which the treatment is started. LNG may inhibit the process of ovulation, fertilization or implantation. However, there is no direct clinical indication that supports these mechanisms. Emergency contraception is effective only before a fertilized egg is implanted because it can’t disrupt an existing pregnancy, i.e., emergency contraceptives are not abortifacient.” (Shohel et al. 2014)

“Kahlenborn and colleagues, in their 2002 publication, summarize early studies regarding the post-fertilization effects of EC (emergency contraception) agents. Based on a combination of theoretical and empirical arguments, the authors argue that the efficacy of EC agents cannot be explained by ovulatory inhibition or the inhibition of sperm transport alone. Thus, they surmise that endometrial effects must also be present.  This position is bolstered by the FDA-approved labeling of Plan B One-Step: “Plan B One-Step works primarily by: preventing ovulation, possibly preventing fertilization by altering tubal transport of sperm and/or egg, [or] altering the endometrium, which may inhibit implantation. Plan B One-Step is not effective once the process of implantation has begun”. It is worth noting that the FDA-approved labeling of Plan B One-Step may allow for the possibility of a post-fertilization effect, even in the absence of supportive data. Computer models intended to clarify the mechanism of action have fallen short, always confirming the effect of ovulatory inhibition, but failing to rule out the possibility of a post-fertilization effect.” (Lewis & Sullivan 2012)

”For the past two decades the scientific community seems to have been burdened with the impetus to prove, in contrast with the typical protocol by which the mechanism of action for a drug is determined, the manner by which a drug doesn’t act by proving “beyond a shadow of a doubt” the manner by which it does act. The authors of this manuscript would be foolish to believe that such a shadow will ever be completely removed from the inquiry at hand, at least until such a time as we have access to a test that might identify the moment of fertilization, as suggested by some writers. However, present evidence provides sufficient motivation to believe that levonorgestrel, used as EC, possesses no clinically relevant effect during the post-fertilization period. (Lewis & Sullivan 2012)

Given the above information, the literature seems to indicate that the primary method of pregnancy prevention for each of these substances occurs pre-fertilization.  However, all 4 substances list alteration of the endometrium or prevention of implantation as possible mechanisms.  Plan-B seems to question this possible mechanism the most throughout the literature, as discussed by Lewis & Sullivan (2012).

Some blogs (Blog 1 & 2, as examples) are loudly declaring that the FDA has stated that none of these 4 substances are abortifacients.  I am not sure what studies the FDA is citing to make this declaration, but there is a simpler explanation of why many people believe these substances can have a post-fertilization mode of action.  It appears that they have gotten their information from the FDA required prescribing information documents of each of these contraceptives. 

Here are quotes from the documents for each of the substances in question.

ELLA

“When taken immediately before ovulation is to occur, ella postpones follicular rupture. The likely primary mechanism of action of ulipristal acetate for emergency contraception is therefore inhibition or delay of ovulation; however, alterations to the endometrium that may affect implantation may also contribute to efficacy.” 

In addition to this statement, information about trials in pregnant rats and primates (not humans) did show that established pregnancies were terminated by the substance in about 40% of the cases.  (Ella Patient Information Leaflet)

MIRENA

“The local mechanism by which continuously released LNG enhances contraceptive effectiveness of Mirena has not been conclusively demonstrated. Studies of Mirena and similar LNG IUS prototypes have suggested several mechanisms that prevent pregnancy: thickening of cervical mucus preventing passage of sperm into the uterus, inhibition of sperm capacitation or survival, and alteration of the endometrium.” (emphasis mine, Mirena Patient Information Leaflet)

PARAGARD

“The contraceptive effectiveness of ParaGard® is enhanced by copper continuously released into the uterine cavity. Mechanism(s) by which copper enhances contraceptive efficacy include interference with sperm transport and fertilization of an egg, and possibly prevention of implantation.” (emphasis mine, Paragard Patient Information Leaflet)

PLAN-B

“Plan B One-Step^® works primarily by:  1) Preventing ovulation.  2) It may also work by: Possibly preventing fertilization by altering tubal transport of sperm and/or egg; or altering the endometrium, which may inhibit implantation” (emphasis mine; Plan-B Website)

Each of the 4 contraceptives in question list prevention of implantation as a possible mode of action in their patient information leaflet.  If you are not an academic with easy access to primary literature, it seems logical that you would draw the conclusion that these substance might have a post-fertilization mode of action to prevent pregnancy.  I mean – you read the information provided by the manufacturer! 

I want to repeat here a quote from above that gives some good food for thought on this topic - ”For the past two decades the scientific community seems to have been burdened with the impetus to prove, in contrast with the typical protocol by which the mechanism of action for a drug is determined, the manner by which a drug doesn’t act by proving “beyond a shadow of a doubt” the manner by which it does act. The authors of this manuscript would be foolish to believe that such a shadow will ever be completely removed from the inquiry at hand, at least until such a time as we have access to a test that might identify the moment of fertilization, as suggested by some writers.” (Lewis & Sullivan 2012)

Truly, after looking at the primary literature, I would not have an ethical issue personally using Mirena, or Plan-B.  The mechanism of action demonstrated in various studies appears to be pre-fertilization.  I do have quite a few questions about Ella, given the animal studies that have shown abortifacient properties in those species.  For both Plan-B and Ella, I also have questions about the safety and possible long term effects of repeated use, but those questions aren’t really relevant to the current question.  However, I very much understand the concern of those without my background in this area of study and without access to primary literature.  Published statements from the manufacturer’s themselves that support the view of Hobby Lobby! 

If one believes that human life begins at the moment of conception and that human life is special and worth protecting, erring on the side of caution seems a responsible path.  

Works Cited

Bhathena, R. K., & Guillebaud, J. J. (2008). Intrauterine contraception: an update. Journal Of Obstetrics & Gynaecology, 28(3), 262-265. doi:10.1080/01443610802042266

BOSWORTH, M. C., OLUSOLA, P. L., & LOW, S. B. (2014). An Update on Emergency Contraception. American Family Physician, 89(7), 545.

Lewis, J. D., & Sullivan, D. M. (2012). ABORTIFACIENT POTENTIAL OF EMERGENCY CONTRACEPTIVES. Ethics & Medicine: An International Journal Of Bioethics, 28(3), 113-120.

Mandelin, E, Koistinen, R, Koistinen, H, Affandi, B, Seppala M.  Levonorgestrel-releasing intrauterine device-wearing women express contraceptive glycodelin A in endometrium during midcycle: another contraceptive mechanism? Hum.Reprod. (1997) 12 (12):2671-2675 doi:10.1093/humrep/12.12.2671

McKeage, K., & Croxtall, J. D. (2011). Ulipristal Acetate: A Review of Its Use in Emergency Contraception. Drugs,71(7), 935-945. doi:10.2165/11207410-000000000-00000

Shohel, M., Mahfuzur Rahman, M., Zaman, A., Nasir Uddin, M., Al-Amin, M., & Mahmud Reza, H. (2014). A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception. BMC Women's Health, 14(1), 1-15. doi:10.1186/1472-6874-14-54

Standford JB, Mikolajczyk RT. 2002. Mechanisms of action of intrauterine devices: update and estimation of postfertilisation effects. American Journal of Obstetrics and Gynecology 187:1699–1708

Blog 1 - The Hobby Lobby Decision: A Summary and Explanation 7/1/14 Love, Joy, Feminism by Libby Anne

Blog 2 - If Hobby Lobby Wins, Pro-Life Christians Lose 6/27/14, Huffington Post by Rev. Richard Cizik

Ella Website – www.ellarx.com

Mirena Website – www.mirena-us.com  

Paragard Website – www.paragard.com

Plan B Website - http://planbonestep.com/hcp/taking-plan-b-one-step.aspx