For the first time, Argentine researchers demonstrated that COVID-19 at least temporarily affects the function of the ovaries in women , which could affect their chances of conceiving naturally or through assisted reproduction techniques and reinforces the importance of ensuring vaccination in that population.
The study was led by scientists from CONICET and the Institute of Biology and Experimental Medicine (IBYME), in the City of Buenos Aires, and was published in the journal “Molecular Basis of Disease”.
The women studied were recruited from assisted reproduction centers and had had COVID-19 3 to 9 months ago. “At this moment, we are evaluating whether these ovarian alterations can be reversed after longer periods, such as 9 to 18 months ,” said the leader of the study, doctor in Chemistry Fernanda Parborell, head of the Ovarian Physiopathology Studies Laboratory at the IByME, which depends on CONICET.
“It is important that couples who have had COVID-19 and are looking for a pregnancy through natural means and cannot achieve it yet, know that it may be due to the infection they suffered months ago and that it is a possibly transitory phenomenon ,” said Parborell, who added that the finding could also help optimize assisted fertility treatment protocols.
The study
IByME researchers evaluated the effect of SARS-CoV-2 infection on ovarian function in women who sought assistance in assisted reproduction centers: 34 control patients and 46 patients recovered from COVID-19 who were asymptomatic or had mild symptoms such as loss of smell and/or taste, sore throat and fever.
The study material was follicular fluids , which are obtained by aspiration to extract the eggs from the ovary and use them in assisted reproduction techniques.
“Oocytes (immature eggs) are in this fluid before ovulation occurs. "The waste material is what we study and is composed of a complex mixture of hormones, cytokines (immune system proteins), metabolites and other proteins released by ovarian cells and that are important for the quality and development of the eggs." Parborell explained.
The researchers verified that IgG antibodies against SARS-CoV-2 were detected in 91% of the follicular fluids of post-COVID-19 patients. “It is very rare to observe immunoglobulins against pathogens in follicular fluids. Furthermore, patients with higher levels of antibodies had a lower number of recovered and mature oocytes,” indicated the CONICET scientist.
The researchers also stimulated a culture of human ovarian cells with follicular fluids and found that those from women who had COVID-19 produced lower levels of three markers that favor pregnancy: StAR, a key protein in ovarian function; Erβ, a hormone or estrogen β receptor essential for egg development; and VEGF, a vascular growth factor that promotes irrigation of ovarian cells. They also verified greater genomic damage in cultures of ovarian and endothelial cells.
“In conclusion, our results describe for the first time that SARS-CoV-2 infection negatively affects the follicular microenvironment (what surrounds the oocyte), which deregulates ovarian function and affects the quality of oocytes in patients recovered from COVID-19 ,” Parborell said.
“Based on the experience we have in the study of ovarian pathophysiology, it is very possible that the ovary will restore its function to normal levels after an appropriate time. Currently, we are carrying out experiments to confirm this and establish the ovarian recovery time after infection,” he added.
Fernando Neuspiller, a doctor with a master’s degree in reproduction from the University of Valencia, in Spain, director of the IVI Assisted Reproduction Center and Member of SAMER (Argentine Society of Reproductive Medicine) and SAEGRE (Argentine Society of Gynecological and Reproductive Endocrinology) agreed with Dr. Parborell that this could be a temporary phenomenon that could be reversed “fairly soon.”
“Those women who had COVID-19 or who had it, we froze their eggs and subsequently did the treatment and transfer of the fertilized egg basically so that they are disease-free from day one. Perhaps some of the ovarian function is modified by COVID-19, but once it is overcome, it is impressive that this event, at least from what we see in the cases we treat, is reversed,” Neuspiller stated.
Yamila Herrero (first author of the work), Natalia Pascuali, Candela Velázquez, Gonzalo Oubiña and Dalhia Abramovich, from IByME and CONICET, also participated in the work; Vanesa Hauk, from the Institute of Biological Chemistry of the Faculty of Exact and Natural Sciences (IQUIBICEN), which depends on the Faculty of Exact and Natural Sciences of the UBA; Ignacio de Zúñiga and Mariana Gómez Peña, from Pregna Reproductive Medicine; Gustavo Martínez, from Fertilis Reproductive Medicine; Mariano Lavolpe, from In Vitro Buenos Aires; Florencia Veiga, from the IVI Assisted Reproduction Center; and Leopoldina Scotti, from IByME, CONICET, and the Northwest Research and Transfer Center of the Province of Buenos Aires (CITNOBA), CONICET, the National University of the Northwest (UNNOBA) and the National University of San Antonio de Areco .
