When faced with infertility, many women adopt, but some continue to try anything to get pregnant. Fertility clinics have cropped up all over the nation, aiding women in their attempts to become pregnant by offering counseling and several tests and treatment options, including in vitro fertilization. However, there are still a few women for whom such procedures do not work.
Doctors and other fertility specialists try to pinpoint the problem, but often, their patients are categorized as "infertile for unknown reasons." However, a recent study at the Hopkins Fertility Center explores a genetic deficiency that may explain why some women simply cannot get pregnant. Dr. Melissa Yates and her group have looked into how a gene, SCARB1, which encodes for a scavenger receptor known as SR-B1, may influence progesterone production, thus affecting a woman's fertility.
Our genes have multiple versions, called alleles, which comprise our unique genome. On a smaller scale, we have single-nucleotide polymorphisms, or SNPs, in which a single nucleotide in a length of DNA differs among people. Understanding SNPs and the variances they cause in people is one of the cornerstones of genetic research.
In this study, Yates explored the SNPs of SCARB1 and found that infertile women with the SNP rs4238001 had a deficiency of SR-B1. "This receptor helps to pick up cholesterol in a number of different tissues," Yates said. "Basically, SR-B1 works in the ovaries, liver and adrenal glands and picks up HDL. It doesn't bind LDL, and in that way, it binds for selective cholesterol uptake, and in women, that's how it works in steroidogenesis."
Women release many hormones that fluctuate during pregnancy. After ovulation, the corpus luteum, which is derived from the ovarian follicle, produces high levels of progesterone to maintain the possible pregnancy. If the egg is not fertilized, the corpus luteum will stop secreting progesterone, and the uterine lining will slough off during menstruation.
A deficiency in SR-B1, then, would inhibit the increase in progesterone necessary to pregnancy. Yates, who regularly sees patients suffering from infertility, explained how her group developed an assay to test the patients for the rs4238001 SNP and found that women with this polymorphism produced lower levels of progesterone from their follicles.
Yates found that other SNPs resulted in varying degrees of SR-B1. For example, patients who were found to have the rs5888 SNP produced more progesterone than other patients. "We don't know if its definitive," Yates said, "but we see that some alleles are more helpful [in becoming pregnant] than others."
When asked if they found a potential "optimal fertility gene," Yates laughingly responded, "that would be pretty awesome, but we don't know it yet." She emphasized the fact that the women who come to the clinic and participate in this study were deemed infertile in some sense. "We don't know what it looks like in the general population yet," Yates said. "We wonder what SR-B1 looks like in people who are usually able to get pregnant."
SR-B1 SNPs and their role in fertility has been studied before. In one model, mice were knocked out for SR-B1 and were found to be infertile. However, the mice regained fertility after treatment with the antioxidant probucol, a drug that had historically been used to lower cholesterol. It was found that probucol lowered HDL, the "good" cholesterol, in addition to LDL, the "bad" cholesterol, and the FDA took it off the market.
However, Dr. Yates and her colleagues believe that probucol may help infertile women produce the necessary amount of progesterone to achieve and maintain pregnancy. They are working to write a clinical protocol for use of probucol in their study.
Currently, infertile women are advised to look into in vitro fertilization to become pregnant, but Yates believes that there may be better treatments. "The best we have to offer is IVF, mainly because we're able to maximize all of the hormones," Yates said. "Hopefully in the future, with this and other causes of infertility, we can make treatments more specific to the person."
She has hope for a relatively young procedure, intra-cytoplasmic sperm injection, or ICSI. "If you inject sperm into an egg, you can fertilize it, so as we go along, we expect more technology that will improve outcomes for a lot of these patients."
As for her study on SR-B1, Yates says that, ideally, the next step would be to look at the receptor in fertile people in the general population and compare it to those of the infertile population. For now, however, Yates reminds her patients in the "infertile for unknown reasons" category that "just because we can't figure out today why you're infertile, doesn't mean that we won't in the future."
