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
