Replies

The link is working well for me. The link you gave is an attempt to argue against the position of Dr DeCook, Dr. Joe McIlhaney and others.

The main question is:

""In the extensive literature we have reviewed, no writer has addressed this very significant question: In a menstrual cycle on the "pill" in which ovulation occurs, what is the histology of the endometrium six days after ovulation (the time of implantation)?""

The articles that support the claim that the combination pills act as abortifacients do not compare women on the pill who ovulate and those who do not. They compare women on the pill and women off the pill.

The driving force on the development of the uterine lining after ovulation is the corpus luteum, the remnants of the follicle that the oocyte developed in. If there is ovulation, the corpus luteum effects over come the effects of the low-dose combination pills. So, if there is ovulation, there is no 'hostile endometrium.' If there is no ovulation, there is no chance of fertilization, so no chance of abortion. Here are the portions of the article which deal with this specific question:

(The website is the American Association of Pro-life Obstetricians and Gynecologists. There are 2 papers, with opposing arguments. Only one addresses the effects of the corpus luteum after ovulation. Please note the date of 1999, so this is not the article your reference is rebutting.)

http://www.aaplog.org/decook.htm
""

Please also see:
Birth Control Pill: Abortifacient and Contraceptive
Hormone Contraceptives Controversies and Clarifications

Authored by four Christian ProLife Obstetrician-Gynecologists
April,1999

Introduction

Recently, there has been some controversy, and serious questions have been raised by sincere individuals who are concerned that hormone contraceptives may have an abortifacient mechanism of action. This paper will help to clarify the issue based on a through review of the available medical literature regarding the mechanism of action of hormone contraceptives. It has been compiled by Board Certified practicing Ob/Gyns, in consultation with Perinatologists and Reproductive Endocrinologists, each being a physician committed to honoring the sanctity of human life from conception. We affirm that as physicians answerable to our Creator and Redeemer, we are responsible to the best of our ability to help, and not intentionally harm, our fellow human creatures. As Christian physicians, we affirm that all life is created by God and that human life is initiated at conception. Fertilization, not implantation, marks the beginning of human life. Disruption of the fertilized egg represents abortion.

The issues of mechanism of action of commonly used hormone contraceptives has threatened to split the pro-life physician community. Review of information currently being disseminated reveals some powerful and well written rhetoric. However, the issue of mechanism of action of hormone contraceptives is not one which will be illuminated by rhetoric. The mechanism of action of any medicine will not change based on how we feel about it, or on who developed it, or on how eloquently it is defended or opposed. How a medication works is a scientific question.

The hormone contraceptives include four basic types: combination oral contraceptives (COCs), injectables (Depoprovera), progestin only pills (minipill, or POPs), and implants (Norplant). In this paper, they will, where convenient, be collectively referred to as the "pill." Most hormone contraceptives are noted to work by 3 methods of action:

1)Primarily, they inhibit ovulation by suppression of the pituitary/ovarian axis, mediated through suppression of gonadotrophin releasing hormone from the hypothalamus.

2)Secondarily, they inhibit transport of sperm through the cervix by thickening the cervical mucous.

3)They cause changes in the uterine lining (endometrium) which have historically been assumed to decrease the possibility of implantation, should fertilization occur. This presumption is commonly known as the "hostile endometrium" theory.

A thorough review of the medical literature uncovers ample data to support the first two methods of action, which are contraceptive actions. (Appropriate references will be found in the sections discussing each type of hormone contraceptive.) However, there is no direct evidence in the literature to support the third proposed method of action. This conclusion is shared by the respected Gynecologic Endocrinology textbook authors Yen and Jaffe. (1) Nevertheless, for the past nearly 40 years, most authors of "pill" related scientific literature have routinely repeated the assumption of a contra-implantation effect by this "pill" primed uterine lining. In light of this large body of literature, some prolife authors have expressed appropriate concerns that hormone contraceptive methods may include an abortifacient action by hindering implantation. These authors have cited data drawn from this scientific literature to support their claims. Closer scrutiny of the medical literature, however, reveals that the scientists are all simply agreeing that the "pill" produces a thinner, less glandular, less vascular lining. We also agree. However, in an ovulatory pill cycle, the estrogen and progesterone levels are, as discussed below, grossly increased for the seven days prior to implantation. The normal biologic response of endometrium to high levels of these hormones is growth of stroma, blood vessels, glands, and glandular secretions to help prepare the lining for implantation.

An extensive review of pertinent scientific writings indicates that there is no credible evidence to validate a mechanism of pre-implantation abortion as a part of the action of hormone contraceptives. On the contrary, the existing evidence indicates that "on pill" conceptions are handled by the reproductive system with the same results seen with "off pill" conceptions, with the exception of increased ectopic rates seen with POPs and Norplant. Not all the contraceptive agents are equally effective, or even equally appropriate, to be used by doctors and patients concerned with the sanctity of life and maternal welfare. The remainder of this paper is a presentation of the current scientific data which will allow doctors and patients who are committed to the sanctity of life from the time of conception to make decisions regarding the use of these agents that his or her conscience can be at peace with. We do not assume that everyone, given the same information, will arrive at a uniform decision. However, for the follower of Christ, discernment based on prayer and the evaluation of factual information in the light of Scripture is the basis of ethical decision making.

Normal physiology

It is helpful at this point to review the basic physiology of the normal ovulatory cycle. Specific endocrinologic details are best found in a text of gynecologic endocrinology. However, in general, after a young woman completes puberty, the levels of estrogen rise and fall twice during each normal menstrual cycle. The pituitary gland releases follicle stimulating hormone (FSH), which causes new, ovum-containing follicles (eggs) to develop in the ovaries during the first half (or follicular phase) of the menstrual cycle. The follicle steadily increases estrogen production, which reaches a peak about one day prior to ovulation. The surge of estrogen stimulates her pituitary gland to secrete another essential hormone, luteinizing hormone (LH), which in turn serves to trigger ovulation (egg release).

Ultrasound can be used to assess the growth and development of the ovarian follicle (cyst around the egg cell) and can indicate the degree of readiness for ovulation.(2) During an ovulatory cycle the usual cyst size varies from 20 to 28 mm. Non-ovulating follicles rarely exceed 14 mm in diameter. Ovulation is associated with complete emptying of the follicular contents in 1 to 45 minutes. After ovulation, the follicle which has released the egg becomes filled with another type of cell, a luteal cell. The luteal cells proliferate under the influence of pituitary luteinizing hormone, (LH), and secrete ever increasing quantities of both estrogen and progesterone.

The follicle (now a corpus luteum) most commonly appears as a smaller, irregular cyst which, if conception has NOT occurred, diminishes in size and ceases to function 2 weeks after ovulation. With subsequent decrease of luteal estrogen and progesterone, the uterine lining (endometrium) is then shed as the menstrual period. However, if conception HAS occurred, the embryo begins, by the time it implants, to secrete another chemical messenger, hCG (human chorionic gonadotropin), which acts like LH to rejuvenate and stimulate the corpus luteum to continue its function until the placenta takes over hormone production 2 months later. The corpus luteum produces, in the six days after ovulation, 10 to 20 times the levels of both estrogen and progesterone seen in a non-ovulatory "pill" cycle. (Preovulatory pill cycle has estradiol level of 25 pg/ml, preovulatory normal cycle has estradiol level of about 40 pg/ml.) During an ovulatory cycle, estradiol reaches a peak of 400 pg/ml during the day before ovulation-a ten to 16 fold increase-and peaks again at 275 pg/ml by day 6 after ovulation, which is the day of implantation. Progesterone values rise from a preovulatory 0.5 ng/ml to a peak of 10 ng/ml by implantation day-a twenty fold rise. (41,42) These high levels act on the lining in these seven days to prepare it for implantation and support of the arriving (via the fallopian tube) living embryo. Corpus luteum function continues until 8 to 10 weeks from ovulation, at which time (noted above) the placenta assumes the burden of producing these hormones to support the growing pregnancy.

In the extensive literature we have reviewed, no writer has addressed this very significant question: In a menstrual cycle on the "pill" in which ovulation occurs, what is the histology of the endometrium six days after ovulation (the time of implantation)? Certainly the hormone milieu and endometrial histology will be different from a menstrual cycle on the "pill" in which ovulation does not occur (i.e.,the typical atrophic, or "hostile," endometrium). The FSH-LH-estradiol surge the day before ovulation, and the resulting corpus luteum formation, with its ten to twentyfold estradiol and progesterone output, should produce significant changes in the endometrium. In a normal menstrual cycle, on the day of ovulation the uterine lining (proliferative endometrium) is not receptive to implantation. Seven days of follicle and corpus luteum hormone output transform it to "receptive." The same follicle and corpus luteum hormone output, when ovulation occurs in a "pill" cycle, should have a similar salutary effect on the pill-primed endometrium. It is highly probable that the so-called "hostile to implantation" endometrium-- heralded (without proof) from the beginning by the "pill" producing companies, echoed (without investigation) by 2 generations of scientific writers, and now adopted (as a scientific fact) by some sincere prolife advocates-- simply does not exist six days after ovulation in a pill cycle. What is currently known about the endometrial response to corpus luteum hormones suggests this conclusion. Research regarding endometrial histology on the sixth day after escape ovulation in "on pill" cycles would add useful information to the current discussion.""

and

""Additionally, as noted above, in an "on pill" escape ovulatory cycle, with the required FSH-LH surge, followed by post ovulatory corpus luteum estradiol and progesterone output, one would expect the endometrium to undergo the usual hormonally related changes favorable to implantation, as in any ovulatory cycle. (The endometrium is sufficiently responsive to physiologically balanced hormones that even the slightly increased estrogen balance in triphasics produces a histologic trend toward secretory pattern.)(40) To have a meaningful discussion regarding the mechanism of action of COCs, and to address the " potential abortifacient" question, a review of the pertinent medical literature is necessary. The following discussion is based on our review.""

and

""The perfect use failure rate most often quoted in the medical literature, including the standardized FDA product labeling of every combined oral contraceptive listed in the PDR is 0.1 pregnancies for every 100 women years (1300 cycles). Therefore, it can be concluded that at times, ALL of mechanisms of action of COCs fail.

Regarding spontaneous abortion rates with "pill" pregnancies.

Spontaneous abortions can be divided functionally into "clinical abortions," i.e., spontaneous loss after pregnancy has been clinically recognized (usually from about 6 menstrual weeks, which is 4 conceptional weeks), and "pre-clinical abortions," loss occurring before that time. Pre-clinical abortions can further be divided into "pre-implantation abortions, those occurring before the conceptus implants 6 days after fertilization, and those occurring after implantation, but before clinical recognition of the pregnancy. There has been no demonstrated effect of COC use on spontaneous clinical abortion rates. (78) The essential abortifacient argument brought against hormonal contraception is that it causes pre-clinical, more specifically, pre-implantation, abortion due to an inhospitable lining, the"hostile" endometrium." The improbability of this entity, based on known follicle and corpus luteum hormone output during an ovulatory cycle, and normal endometrial response to these hormones, has been discussed earlier in this paper.

To look at the controversy from another direction, do "pill" pregnancies have similar outcomes as non-pill pregnancies? Clinically, the answer is "yes." There is no data to indicate higher clinical spontaneous abortion rates or more problems in ongoing pregnancies. But is there increased loss evident with "pill" pregnancies? From the clinical side, the answer is "no." (78) From the pre-clinical, especially the pre-implantation perspective, the answer must be sought by evaluating indirect data, since there is no direct data regarding these loss rates available for users of COCs. Most studies evaluating efficacy of COCs only measure clinically evident pregnancies as an end point. There is scarce literature about ovulation rates on COCs, although more than 40 such studies were reviewed in preparing this paper. Of the COC studies that evaluated ovulation, fertilization and pregnancy rates are almost never evaluated. The reason for this should be obvious: if a patient in a COC study is told that she has ovulated, she will avoid exposure to sperm, thus preventing an unwanted pregnancy.

Concerning the outcome of "on pill" ovulations

The first requisite in evaluating this question is to establish a reliable unintended ovulation rate in perfect (compliant, i.e., no missed pills) COC users. In this pursuit, 25 studies were reviewed (several papers contained more than one study). (ref 59 through 76) These studies used a variety of common COCs, including triphasics, and were about evenly split between the newer very low dose pills(20 mcg estinyl estradiol), and the current standard low dose pills(30 to 35 mcg ethinyl estradiol). Eighteen studies including 3799 cycles showed zero ovulations. Seven studies including 2910 cycles showed 8 ovulations. (Ovulation was indicated by ultrasound and serum chemical markers.) Combining these gives a practical working number of 8 ovulations in 6709 cycles, which equals 15.5 ovulations in 13,000 cycles, (a figure used to simplify the arithmetic done below). This is not a scientific metanalysis. Rather, it is a pragmatic figure, using the referenced peer-reviewed data, that will help provide an informed perspective on the question of pre-implantation loss.

The next necessary information concerns the unintended pregnancy rate on compliant use of COCs. This is well established in the Hatcher table (8) at 0.1 pregnancy per 100 women years, which equals one pregnancy per 1,000 women years, or one pregnancy in 13,000 cycles by compliant pill takers. Thus we have, in l3,000 cycles, l5.5 ovulations (from the previous paragraph), and one pregnancy.

Finally, the cervical mucus factor must be considered. The marked change in cervical mucus under the influence of progestins is recognized as a substantial factor in contraceptive effectiveness of the "pill." As reviewed by McCann, (6) studies of cervical mucus changes on the POPs, which contains only half the dose of progestin found in the COCs, found the mid cycle mucus to be greatly reduced in volume, increased in viscosity and cell content, with altered molecular structure. (52, 53, 54) The effect is a mucus with low spinnbarkeit and poor ferning. This is found to result in little or no sperm penetration in 70-80% of cases. (53) Even in the rare cases when penetration does occur, sperm motility is reduced.(55, 54, 56, 57, 58) One study noted almost total absence of sperm in the uterine cavity of the progestin treated group, while sperm were present in the uterus of 18 of 19 controls. (55) COCs, with twice the progestin dose of POPs, would produce mucus with similar, if not greater sperm impedance. (Although COCs also contain an estrogen, ethinyl estradiol, they block follicle activity so well that the actual preovulatory serum estradiol levels on the "pill" are less than normal, i.e.,25 pg/ml vs the normal 40 pg/ml. This level will have negligible influence on improving cervical mucus.) In the normal cycle, the pre-ovulatory FSH surge will immediately produce an estradiol peak of 400 pg/ml, quickly resulting in production of the optimum fertility enhancing mucus. In an ovulatory "pill" cycle, this estradiol peak almost certainly will override, to some degree, the progestin induced sperm blocking effect on the cervical mucus. It is not known how quickly, or to what degree, this override might take place. Reproductive endocrinologists indicate that ovulation takes place within 12 to 24 hours after the LH-FSH surge with its accompanying estradiol peak, and that the newly released egg can only accept fertilization for about l2 hours before it becomes resistant. This leaves a window of about 24 to 36 hours for the transformation of the impenetrable cervical mucus to fertility-favorable mucus which would allow release and transport of sperm to the distal portion of the fallopian tube to fertilize the egg. (And this assumes that sufficient numbers of viable sperm are present in the cervical mucus at the time the mucus becomes favorable.) We know that the cervical mucus factor adds significantly to the contraceptive effectiveness of the pill--although to what extent in an ovulatory cycle can only be estimated, since there have been no specific studies done to give us numbers.

The available data referenced in this discussion has, then, yielded this information: 13,000 cycles of compliant COC use results in 15.5 ovulations, and one ongoing pregnancy. The basic question in the entire "pill" controversy is, "What happened to the other 14.5 eggs?" Were they the victim of an "inhospitable endometrium"(whose existence in an ovulatory cycle is very questionable), or can they be accounted for in other ways? Let us start with the 15.5 ovulations noted above. Available data indicate that 10 to 15% of our population is infertile.(41, p 809) Of the original 15.5 eggs, This leaves 13.5 eggs available for possible fertilization and ongoing pregnancy. One could simply take the 13.5 eggs available for fertilization, apply the normal human fecundity table of 25% per cycle (the fecundity table requires optimum conditions: normal fertility in the man and woman, and correct timing of coitus). (28) We would expect 3.3 pregnancies, IF the cervical mucus is favorable, the viable sperm are present, and the timing is right. Referencing the previous paragraph, cervical mucus factors block sperm 80 to 90% of the time in non-ovulatory studies. IF adequate numbers of viable sperm can get free and make it to the waiting egg within the 36 hour receptivity window just 33% of the time, one egg might be fertilized to become an ongoing pregnancy. We don’t know about the sperm and timing, and the cervical mucus is probably not optimum. If one of these 3.3 remaining eggs is fertilized and thrives, this equals the known ongoing pregnancy rate seen in compliant COC users: One per 1,000 woman years (13,000 cycles) of use. The fate of the l5.5 eggs can also be considered from other available data. Again, the 10 to l5% infertility rate leaves 13.5 eggs available for possible fertilization. Recent critically reviewed data indicates that from fertilization to 6 weeks, spontaneous pregnancy wastage is 73%. (26, 27) This leaves 3.5 eggs available for fertilization and ongoing pregnancy. As above, considering mucus, sperm, and timing factors, one egg might be fertilized to become an ongoing pregnancy. This again equals the known pregnancy rate on compliant COC usage: per 1,000 woman years (13,000 cycles) of use. This exercise in arithmetic is not meant to be a statistician’s scientific proof text. It is rather an overview of COC unintended ovulation rates and subsequent ongoing pregnancy rates using available peer-reviewed data to account for the eggs in question.

A recent study by specialists in reproductive technology found, with genetic sampling of morphologically normal embryos, that 24 of 50 had chromosomal abnormalities, and would likely not survive. (79) Gift procedures, introducing multiple viable eggs, along with good sperm, into the fallopian tube at the optimum time, with optimum endometrium, only yield a 30% success rate. 30% of failed fertilization is due to faulty sperm. There are evidently many naturally occurring reasons for preimplantation loss.

Considering the above information on ovulatory related hormone influences on the endometrium, "on pill" ovulation rates and pregnancy rates, the cervical mucus factor, and known data on human fecundity, fertility, and spontaneous loss rates, it can be appreciated that there is no need to postulate a pill-induced preimplantation abortion phenomenon to explain why 15.5 eggs produce one ongoing pregnancy. Known and natural causes can account for the numbers.

Concerning Ectopic Pregnancy and the "Pill"

If COCs are abortifacient in nature by causing the conception not to implant in the uterine cavity, then ectopic pregnancy rates should be at least equal to that in the normal population. One of the well-studied effects of progestins on the fallopian tube is to decrease motility and cilia action, which would inhibit a fertilized ovum from proceeding into the uterine cavity. Therefore, it would be reasonable to expect an even higher ectopic pregnancy rate than the normal population (2% of all clinically recognized pregnancies). The literature, at this time, does not show an increased ectopic rate per pregnancy for COCs over non-users.

Any contraceptive method decreases the overall ectopic rate, simply by way of decreasing the number of pregnancies that occur at all. A rough estimate of the numbers involved can be calculated using generally accepted data and simple arithmetic: Using the table of Hatcher (8), and assuming "perfect" (correct, consistent) use for COCs, sympto-thermal method, and condoms, three matched groups of l00,000 women would experience l00 unintended pregnancies on COCs, 2,000 unintended pregnancies with sympto-thermal method, and 3,000 unintended pregnancies with condoms. Using the current figure of 2% ectopic ratio (9), these pregnant women would experience 2 ectopic pregnancies with COCs, 40 EP with sympto-thermal method, and 60 EP with condoms. Given the potential maternal mortality, morbidity, and damage to fertility with ectopic pregnancy, and the absence of any demonstrated increase in abortion due to COC endometrial effect, one might ask if it is ethical to withhold or discourage the option of COCs for the woman seeking contraceptive information. Certainly this pertinent information should be considered as part of adequate informed consent. ""