Parasitic Worms Point to Importance of Immune System for Reproduction
Steady readers of these pages know that we here at CHR are always surprised how many of our colleagues consider the immune system irrelevant to reproductive success in women. With the implanting fetus being a so-called semi-allograft (i.e., being half paternal), the fact that embryos are not automatically immunologically “rejected” by the maternal immune system, is really a miracle of nature. Immunological tolerance of the implanting embryo by the maternal immune system, therefore, can be viewed as proof that the maternal immune system must play a crucial role in human reproductive success.
There are, of course, many other hints that this may be the case. A recent study in the prestigious journal Science, however, offers a completely new, and interesting, set of facts (Blackwell et al., 2015;350:970-2). The study was based on the fact that the human fetus and parasites have much in common: both are, what the Science writer Mitch Leslie called interlopers in a commentary to the paper on November 19, 2015. Interlopers need strategies to induce immunological tolerance that allows them to survive. Parasites, therefore, elicit some of the same immunological responses that one can observe in mothers during early pregnancy.
Blackwell and colleagues, therefore, wondered whether parasitic infections might not be able to facilitate the occurrence of pregnancy. To test this hypothesis, the investigators traveled all the way to the Amazon rain forest in Bolivia, and investigated a local indigenous population, known to be frequent carriers of Ascaris (the giant roundworm) and hookworms. When looking at the fertility of the women in this tribe, the investigators made unexpected observations: Women infected with hookworms demonstrated negative effects on their fertility, like increased age at first birth, prolonged inter-pregnancy periods and, consequently, gave birth to fewer children in comparison to uninfected local controls. In contrast, those infected with Ascaris demonstrated quite amazing improvements in all fertility parameters, like younger age at first birth, shortened inter-pregnancy intervals and such women on average had two more children over their lifetimes than controls.
Dr. Blackwell will give a lecture in February 2016 for CHR’s monthly Grand Rounds.
The investigators speculated that Ascaris reduces inflammation, thereby promoting conception and implantation, and are currently performing follow up studies to isolate the immune/inflammatory pathways that may be responsible for these findings.
We are here reporting on this study for three reasons: First, because the study, as already noted, reemphasizes the obvious importance of the immune system for successful reproduction. Second, if the authors are correct and Ascaris is effective by initiating anti-inflammatory pathways, this finding would further support results recently obtained by CHR investigators in infertile women, which demonstrated the importance of inflammatory rather than autoimmune pathways in predicting IVF outcomes (discussed in detail in last month’s VOICE).
Third, because this study would suggest new infertility treatment options with either anti-inflammatory medications or even through immunization with epitopes that elicit immune system responses similar to Ascaris. In addition, the negative effects caused by hookworm infections could potentially be explored to develop new contraceptive options.
Norbert Gleicher, MD, CHR’s Medical Director and Chief Scientist was, indeed, quoted by Mitch Leslie in his commentary in Science in that regard (though his affiliation was erroneously listed only as Rockefeller University.
This is a part of the December 2015 issue of CHR VOICE.
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.
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