Women who are unable to conceive undergo various fertility treatments. Another reason for infertility in women appears to have surfaced. According to a study led by scientists of the Yale University Medical School, New Haven (USA) a genetic variation is responsible for sub-fertility in women and makes them less likely to respond to ovarian stimulating hormones during fertility treatment.
The authors have apparently alleged means to recognize such women and construct personalized fertility treatments overcoming the problem caused by the genetic abnormality. An abnormal hormone receptor was supposedly identified on cells surrounding oocytes (eggs) in a few women.
Dr Maria Lalioti, as assistant professor in the Department of Obstetrics Gynecology and Reproductive Sciences at Yale, added, “When a woman undergoes in vitro fertilisation, she receives medication called Follicle Stimulating Hormone to produce more than one oocyte, which is the normal production each month. Cells called granulosa cells, which surround the oocyte, receive the FSH; these cells excrete other factors that ‘feed’ the oocyte. The granulosa cells have proteins present on their surface called FSH receptors (or FSHR) and it is these proteins that stick to the FSH and then carry signals into the cell’s interior. When we looked at a portion of these granulosa cells in the laboratory we saw that in some women, who produced very few oocytes, there were some receptors that lacked a piece of the protein, although there were still other, normal FSHR in the women’s cells.”
The authors assume that this abnormal receptor hinders the function of normal receptors. These normal receptors were also claimed to be present, further causing affected women to respond less well to Follicle Stimulating Hormone (FSH). The FSH may be provided to women undergoing fertility treatment in order to stimulate the production of more than one oocyte.
The scientists noted an absence of the sequence of protein exon 2 in the abnormal FSHR. The exon 2 is believed to be a crucial part of the protein, binding the FSH. It was highlighted that FSHR with the exon 2 deletions was probably discovered in only women aged younger than 35 years with a poor response to FSH. They seemed to yield less than four oocytes in a follicle stimulating cycle.
Dr Lalioti shared, “We produced the normal and abnormal protein in the lab in a different type of cell called HEK293 (Human Embryonic Kidney) which is a common cell type used in the labs to examine properties of proteins. We saw that when the abnormal receptor was present, the normal one could no longer work as well as it does when it is the only protein present. The receptor is normally present on the cell surface in order to meet and bind FSH, and it needs to go through a number of cellular checkpoints inside the cell that assure the quality of the protein presented on the surface. We saw that the abnormal receptor remains longer in one of these checkpoint compartments, indicating that the cell has detected a problem and is trying to correct it. In this way the abnormal FSHR can contribute to an abnormally low response to stimulation in certain women undergoing IVF.”
An association has been seemingly developed between genetic variation and sub-fertility. The authors affirmed that women with sub-fertility report a normal menstrual cycle and represent as patients with unexplained infertility in various fertility centers. An ovarian stimulation defect can be determined before the first IVF cycle of such women.
FSH is claimed to be the only available medication at present, possibly stimulating ovarian response. Their study seems to present the reasons for women to not positively respond to this medication. But they ascertain that the discovery of other medications may aid in overcoming the receptor for FSH after experimenting on these women. Whether implementing higher doses of medication can be proved beneficial or not still continues to be a mystery for the investigators. Also, there is some previous analysis determining lower FSH to be more beneficial.
The results of the study ascertain the mechanism behind some young women having a poor response to FSH as it may enhance further experiments and treatments of these women. The investigators were seemingly unable to find the number of women with genetic variation. After thoroughly scrutinizing Dr Lalioti possibly detected two out of five women with the genetic variation.
Further analysis will be commenced to ascertain the FSHR signaling mechanisms within the cell. The scientists also aim to observe the way newly developed drugs might bypass the problems created by the genetic abnormality. A sub-group of patients may be provided with personalized treatments in the near future.
The study was presented at the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome.