Some weeks back, I came across a case report published in 1999 in the journal Ultrasound in Obstetrics and Gynecology [1]. It presented a twin pregnancy wherein one of the fetuses seemed to be at a younger developmental stage in its mother’s womb compared to its sibling.

It wasn’t the first time that I had stumbled on a report which detailed a discordance in the growth of a fetus in a twin pregnancy. In fact, cases of growth discordance in multiple pregnancies are not uncommon and may be due to a number of problems such as the placenta’s inability to adequately support the development of more than one fetus, twin-to-twin transfusion syndrome whereby blood is disproportionately transferred from one twin to the other, or other disorders which may as easily occur in single pregnancies (congenital infection, aneuploidy, etc). However, the 1999 case report observed that the twin pregnancy was uneventful and resulted in the delivery of live healthy babies. It concluded that a phenomenon known as superfetation had occurred.

Superfetation is the onset of a subsequent pregnancy during an ongoing pregnancy; a new pregnancy during an initial pregnancy. It happens when there is fertilization of an ovule by a sperm cell while a conceptus is already present in the womb. Intriguing, isn’t it? I thought so and dug deeper in the literature to realize that superfetation had actually been extensively reported in animals [2].

The phenomenon of superfetation in animals has long been speculated as far back as fourth century B.C by Aristotle. Aristotle came to this thought when he observed that hares often gave birth to litters which comprised sets of healthy and imperfect offsprings. He deduced that the imperfect offsprings were younger ones who had spent less time in their mother’s womb—a direct consequence of superfetation. In effect, Aristotle was supposing that the younger offsprings were from a litter which was the result of the second pregnancy.

The badger, American mink, panther, buffalo and swamp wallaby are a few examples of mammals in which superfetation is well documented. Last year, a paper published in Nature Communications reported that superfetation frequently occurred in the European brown hare, even postulating that it may actually be an evolutionary adaptation [3]. For this reason, it is probable that many more mammals may be accustomed to superfetation.

While there is evidence that superfetation may indeed be part of the reproductive processes of certain animals, in humans, it is in all likelihood a rare reproductive abnormality [2]. In other words, it probably occurs by accident. Because for superfetation to occur, a number of things must happen—things that a woman’s reproductive cycle is intrinsically programmed to prevent.

First, for any pregnancy to occur, an ovule must be present. And for an ovule to be present, ovulation must have taken place. Therefore, for superfetation to be possible, ovulation must be triggered during an ongoing pregnancy. And this is a major stumbling block right there. While ovulation happens every month in a fertile woman, it is normally impeded during pregnancy. During the early stages of pregnancy, this is due to the corpus luteum, the surrounding tissue from which the ovule is shed during ovulation. It remains for a couple of days and releases hormones which ultimately prevent further ovulation. If implantation of a conceptus then occurs, the corpus luteum stays for longer still, actively secreting more hormones. Eventually this endocrine role is taken over by the placenta. Therefore, strictly speaking, ovulation can only occur when neither the corpus luteum nor the placenta is present.

Pregnancy also requires the fertilization of the ovule with a sperm cell. This means that semen from the male must be able to attain the ovule in the female’s oviduct. When a woman is pregnant however, a mucus plug is formed in the cervix, blocking the passage of sperm. This mechanism prevents semen from passing through the pregnant uterus, let alone allowing it to reach the oviduct. The mechanism is an important measure against microbes contained in semen which can cause venereal diseases to the fetus. It also prevents the possibility of superfetation.

Finally, a viable pregnancy also requires proper implantation to occur. And for superfetation to occur, the conceptus needs to implant in a pregnant uterus. Implantation is only possible in a delicate and specific environment controlled by different hormones though. Under normal conditions, the appropriate uterine environment is catered for in a woman who is ovulating rather than in one who is pregnant. In addition, space is also an issue in the crowded already-occupied uterus!

In order for superfetation to occur in humans, therefore, it would appear that three seemingly impossible things need to happen: ovulation must take place during an ongoing pregnancy, semen must somehow find its way through the blocked cervix to the oviduct, via the occupied uterus and finally, the conceptus has to successfully implant itself in an unsuspecting already-occupied uterus. The odds of all three of them happening are without doubt extremely small as reflected by the very occasional reports of superfetation in humans in the medical literature.

It should not be surprising then, that reports of superfetation in humans are more commonly associated with women who have undergone fertility treatments. At least this is what I found when during my digging. A case report published in 2005 in the The Journal of Pediatrics, for instance, describe how a 32-year-old woman who had undergone embryo transfer later became pregnant with twins and one additional growth-discordant fetus [4]. Initially, two out of the three embryos transferred to the woman’s uterus implanted themselves and a viable twin pregnancy was pronounced. The third embryo did not develop into a fetus. However, a triple pregnancy was discovered around five months later, when a third smaller fetus was seen by ultrasound. This fetus was deduced to be around three weeks younger than its siblings. This led to the conclusion that there had been a subsequent fertilization and implantation following the successful double implantation from artificial insemination.

During fertility treatments, it is hoped that a woman’s reproductive cycle will come to terms with events that it normally would not have to go through. Taking the above case to illustrate, three embryos were artificially transferred into the woman’s uterus. The norm however, is one ovule per cycle and thus one embryo for implantation—not three! But when the human body is faced with the unusual aspects of pregnancy brought about by artificial reproductive technologies, some mechanisms are more prone to go astray. For example, it is documented that a normal ovulatory response can result in following cycles of controlled ovarian hyperstimulation even if an early pregnancy is present [5].

While to me the phenomenon of superfetation seemed so amazing that I decided to write a blog post about it, I’m not so sure if superfetation is looked upon with the same awe by the girls. Let me know in the comments.

References:

[1] Tuppen, G.D., Fairs, C., de Chazal, R.C. & Konje, J.C. Spontaneous superfetation diagnosed in the first trimester with successful outcome. Ultrasound in Obstetrics and Gynecology 14, 219-221 (1999).

[2] Roellig, K., Menzies, B.R., Hildebrandt, T.B. & Goeritz, F. The concept of superfetation: a critical review on a ‘myth’ in mammalian reproduction. Biological Reviews

[3] Roellig, K., Goeritz, F., Fickel, J., Hermes, R., Hofer, H. & Hilderbrandt, T.B. Superfetation in mammalian pregnancy can be detected and increases reproductive output per breeding season. Nature Communications 1:78 (2010).

[4] Harrison, A., Valenzuela, A., Gardner, J., Sargent, M. & Chessex, P. Superfetation as a cause of growth discordance in a multiple pregnancy. The Journal of Pediatrics 147:2, 254-255 (2005).

[5] Dmowski, P.W., DeOria, L. & Rana, N. Embryo implantation during menstruation in the absence of adequate estradiol and progesterone support, with subsequent normal response to ovulation induction and superfetation. Fertility and Sterility 68:3, 538-541 (1997).

Image credits: Photo 1: Ovary about to release an ovule (credit: Maksim from Wikipedia); Photo 2: Uterus at third to fourth month of pregnancy (credit: Magnus Manske from Wikipedia)

About the Author: Khalil A. Cassimally is a science student by day and science blogger and community blog manager at Nature Education by night. He writes about the science that gets him all excited. He also tweets @notscientific.

The views expressed are those of the author and are not necessarily those of Scientific American.

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