OVARIAN RESERVE

Response to stimulation in IVF may predict longer term health risks

Response to stimulation in IVF may predict longer term health risks

Low ovarian reserve with few eggs collected associated with a higher risk of chronic disease.

A follow-up study of almost 20,000 young women who had a first cycle of IVF in Denmark between 1995 and 2014 indicates that those who responded poorly to treatment, with few eggs collected, are at a significantly increased risk of later age-related diseases.

The findings, according to investigator Mette Wulf Christensen from Aarhus University in Denmark, suggest an “association with early ovarian ageing and an accelerated ageing process in general.”

The results, she explains, are consistent with what we know so far about early menopause, which has been shown in several studies to be associated with an increased risk of cardiovascular diseases, osteoporosis and mortality.

Identifying women at risk of early menopause may thus allow early preventive health initiatives in terms of a healthy lifestyle,” says Christensen.

This is the first time that the yield of eggs in IVF as a measure of ovarian ageing — and thus as a risk predictor of age-related ill-health and mortality — has been investigated in a large-scale cohort study. The results were presented online by Ms Christensen, a PhD student, at the virtual Annual Meeting of ESHRE.

The study was based on the national registries of Denmark in which each individual has their own identifying number, thus allowing cross-linkage between various registries of health outcomes and treatments.

In this case women below the age of 37 who had a first cycle of IVF or ICSI in Denmark between 1995 and 2014 were divided into one of two groups according to their response to ovarian stimulation: those who had produced five or fewer eggs for collection, defined as “early ovarian ageing“; and those who responded normally with at least eight eggs. The number of eggs harvested was thus used as a marker of ovarian reserve. There were 1,234 women in the former group, and 18,614 in the latter.

During the six-year average period of follow-up, the incidence of chronic disease in the two groups was analysed from the cross-linked registry data, providing a real-life estimate of risk for cardiovascular disease, osteoporosis, type-2 diabetes, cancer, and all-cause mortality.

Results showed that women in the early ovarian ageing group had an increased overall risk (by 26%) of all-cause disease when compared to those with a normal ovarian response. This higher risk was statistically significant, and evident in cardiovascular diseases (39% higher) and osteoporosis (more than double).

The two groups were also cross-checked with the “early retirement benefit” register, in which the early ovarian ageing group were also more likely to be listed.

The risk of cancer, other age-related diseases and all-cause death was not significantly different.

Commenting on the implications of the results, Ms Christensen said that, although the common biological mechanisms behind ovarian and general ageing are “somewhat obscure,” the data from this study demonstrate that young women with early ovarian ageing — defined as low oocyte output after FSH stimulation — have an increased risk of age-related morbidity and possibly mortality, “and strongly support the hypothesis that low ovarian reserve may be a useful marker of later health problems.”

Counseling this group of patients at fertility clinics, she added, “may, therefore, be important for introducing preventive measures such as lifestyle changes or the use of HRT to reduce the adverse health risks which follow an earlier menopause.”

Source: European Society of Human Reproduction and Embryology.

Female hormone in hair could predict response to ovarian stimulation for IVF

Female hormone in hair could predict response to ovarian stimulation for IVF

The prospect of a non-invasive test of ovarian reserve is a little closer following results from a study showing that measurement of a fertility hormone can be accurately taken from a sample of human hair.

Anti-Mullerian hormone — or AMH — has become a key marker in the assessment of how women may respond to fertility treatment.

The hormone is produced by small cells surrounding each egg as it develops in the ovary, and is thus seen as a measure of ovarian reserve. Although studies have not correlated AMH levels to a reliable chance of live birth (nor to forecasting the time of menopause), AMH measurement has become an intrinsic marker in assessing how a patient will respond to ovarian stimulation for IVF — as a normal responder, poor responder (with few eggs), or over-responder (with many eggs and a risk of ovarian hyperstimulation syndrome, OHSS).

AMH is presently measured in serum taken from a blood sample drawn intravenously. The readings represent a measurement at a short moment in time and are relatively invasive to complete.

Now, a new study presented at the online Annual Meeting of ESHRE has tested the quantification of AMH from human hair and found it to be a less invasive and a “more appropriate representation of hormone levels” than from an “acute” source like serum.

The results are presented this week in a poster from PhD student Sarthak Sawarkar, working in the laboratory of Professor Manel Lopez-Bejar in Barcelona, with collaborators from MedAnswers Inc in the USA.

The study, which still continues, now reports results from 152 women from whom hair and blood samples were routinely collected during hospital visits. AMH measured in serum from the same subjects was used to provide a control, as was an ultrasound count of developing follicles in the ovary (AFC) as a further measure of ovarian reserve.

“Biologically relevant” AMH levels were successfully detected in the hair samples, with levels declining with patient age, as expected. As ovarian reserve declines with age, so do AMH levels. The AMH levels from hair strongly correlated with both serum levels and AFC.

It was also seen that the hair test was able to detect a wide range of AMH levels within individuals from a similar age cohort, suggesting a greater accuracy than from a single blood sample.

Hormones accumulate in hair shafts over a period of months, while hormone levels in serum can change over the course of hours.

“So hair,” explain the authors, “is a medium that can accumulate biomarkers over several weeks, while serum is an acute matrix representing only current levels. While hormone levels in blood can fluctuate rapidly in response to stimuli, hormone levels measured in hair would represent an accumulation over several weeks. A measurement using a hair sample is more likely to reflect the average hormone levels in an individual.”

Among the other advantages of a hair test, the authors note that hormone levels are assessed non-invasively, which reduces testing stress and offers a less expensive assay. Testing can be done without visiting a clinic, and thus makes this type of test available to a broader range of women.

“Finally,” explains Mr Sawarkar, “as hair offers a look at the long-term accumulation of hormones, this measurement may allow a better understanding of an individual’s hormone levels — unlike blood-based assays, which can only measure the hormone at the moment of the testing.”

AMH has so far had an important — though sometimes controversial — role in reproductive medicine. Thus, while its role as a measure of ovarian reserve in predicting response to ovarian stimulation for IVF now seems beyond question, there has been doubt over its broader application as a measure of female fertility in the general population.

Commenting on the biology of the test, Mr Sawarkar explains that hormones are incorporated into the matrix of hair before the growing hair reaches the skin surface, thereby allowing an accumulating measurement of hormone concentration.

Story Source: European Society of Human Reproduction and Embryology

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