ESHRE appeals to national societies to spread awareness about oocyte donation

The European Society of Human Reproduction and Embryology (ESHRE) has created an oocyte donation brochure DONATION OF OOCYTES in collaboration with the Council of Europe European Committee on Organ Transplantation (CD-P-TO).

ESHRE is encouraging national societies across Europe to translate the publication into their national languages. Composed by internationally recognized experts, the patient brochure on oocyte donation is a guide for women to support informed decisions about donating oocytes.

Many women are unsure whether it is safe or not to donate oocytes and are interested in knowing the future implications of such donations. This guide will provide clear, accurate and balances information about the cause.

To translate the guide into regional language first seek permission with the Council of Europe who holds the copyright of the publication. This can be done by sending an e-mail to publications.info@edqm.eu where you will have to specify your intention and the language of translation.

DONATION OF OOCYTES Brochure

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News from ACOG 2018: Unexplained infertility may be an indicator of decreased ovarian reserve even in young women

Despite advances in diagnostic modalities in the infertile couples, the cause of infertility remains largely unexplained in 25% to 30% of couples. The treatment in these couples remains largely empirical.

The result of a small study presented at the ACOG 2018 by, Dr. Andrea Starostanko MD and Dr. Jonathan Ayers MD from Saint Joseph Mercy Hospital Department of Obstetrics and Gynecology, Ann Arbor, MI suggests that even in young women with unexplained infertility (UI) ovarian reserve should be evaluated as part of initial work up.

Institute for Reproductive Health

They looked at data from 343 nulligravid couples (18-34 years) who were unable to conceive after unprotected coitus for a period of 12 months. The couples underwent tubal patency test, ovulation study and anatomic status by mid-cycle TVUS, comprehensive semen analysis, and assessment of Decreased Ovarian Reserve (DOR) with serum Anti-Mullerian Hormone (AMH).

A cause of infertility was found in 142/343 (41%) couples with anovulation in 30%, anatomic abnormality in 9% and male factor in 6%.  In 201/343 (59%) of couples, no probable cause could be identified.

In these couples with UI, 118/201 women had serum AMH levels below the 95 percentile of age-appropriate value and in nearly 25% of women below the age of 35(53/201), the values were < 1.5.

The researchers concluded that: 

All women with UI should be investigated for ovarian reserve during the initial workup, irrespective of their age

Women who are diagnosed with DOR should seek consultation with a specialist for further treatment options

DOR may also be a harbinger of premature menopause and associated cardiovascular complications  

Abstract

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North American Menopause Society (NAMS) video series about important midlife health topics: The Timing Hypothesis of HRT

The North American Menopause Society is proud of its comprehensive video series for clinicians about important midlife health topics. All the interviews in the series are hosted by NAMS Board of Trustees Member and Immediate Past President Dr. Marla Shapiro, a Canadian physician, who led this exciting initiative. Dr. Shapiro is also the medical consultant for CTV News.

In this latest video, The Timing Hypothesis, Dr. Shapiro interviews Dr. Peter Schnatz, Past President of NAMS and Associate Chairman and Residency Program Director in the Department of Obstetrics and Gynecology at the Reading Hospital in Reading, Pennsylvania. Dr. Schnatz discusses the benefits of starting women on hormone therapy at the beginning of the menopause transition, along with the cardiovascular health advantages.   

The ELITE:Early Versus Late Intervention Trial With Estradiol also affirms the timing hypothesis in relation to timing of estradiol administration, when a beneficial cardiovascular effect is only seen in women with early, but not later menopause.

Early menopause ups the risk of developing type 2 diabetes

Women who have an early natural menopause have 2.5 times the risk of developing type 2 diabetes as compared to women who have normal menopause reports the results of a large population based study published online July 18, 2017 in Journal Diabetologia.

Taulant Muka, MD, PhD, of Erasmus University Medical Center, Rotterdam, Netherlands, and colleagues write, "In this large population-based study of postmenopausal women free of type 2 diabetes at baseline, we showed that early onset of natural menopause is associated with an increased risk of type 2 diabetes, independent of potential intermediate risk factors for type 2 diabetes (including body mass index [BMI], glucose, and insulin levels) and levels of endogenous sex hormones and SHBG [sex hormone-binding globulin]."

Menopause is a major transition point in women’s life and declining estrogen levels predispose her to increase risk of cardiovascular disease. But, few studies have examined the association between age at menopause and risk of developing type 2 diabetes. Few cross-sectional studies have yielded conflicting results because beside declining hormonal levels, menopausal weight gain, increase in visceral fat and impaired glucose metabolism may also play a part.

This study examined data from Rotterdam study and recruited 3639 women in the final analysis. The Rotterdam Elderly Study is a prospective cohort study in the Ommoord district in the city of Rotterdam, the Netherlands aimed to investigate the risk factors of cardiovascular, neurological, ophthalmological and endocrine diseases in the elderly.

All the women in the current study have attained natural menopause and did not have diabetes at the time of enrollment. The mean age at of woman  was 66.9 (9.6) years, the mean age at natural menopause was 50.0 (4.4) years with median time elapsed since menopause was 15.0 years. The women were stratified into 4 groups according to age at menopause: premature (< 40 years), early (40–44 years), normal (45–55 years), or late (> 55 years).

An analysis of the study cohort showed that 348 women (9.6%) developed type2 diabetes during a median follow up of 9.2 years after adjusting for confounders like age, BMI, glucose and insulin levels, smoking, HRT and genetics. Late menopause is a significant protective factor as compared to premature and early menopause.

Women with late menopause were protected against developing diabetes, and the risk increased as the age at natural menopause decreased. The risk was nearly 4 times higher in women with premature menopause (HR, 3.7)  twice   in women with early menopause (HR, 2.4) and 60% more in women with normal menopause (HR, 1.6; P < 0.001) .

For each 1year delay in onset of menopause, the risk of developing diabetes was lowered by 4% (HR, 0.96).

The authors could not account for the mechanism linking age at natural menopause with development of type 2 diabetes. Earlier data have shown that natural early menopause is a sign of not only reproductive aging but also early somatic aging and all its cardiometabolic consequences. Hence, early menopause can be a good predictor of future general health including type 2 diabetes.

But, the results remained the same after adjusting for the shared genetic factors, so the pathophysiology is unclear and requires more studies in future.

The authors concluded,” The Early onset of natural menopause is an independent marker of type 2 diabetes risk in postmenopausal women. Future studies are needed to examine the mechanisms behind this association and explore whether the timing of natural menopause can add value to diabetes prediction and prevention.”

The full text can be accessed here.

Menarche ≤11 years and Nulliparity is a risk factor for Premature and Early Menopause.

courtesy: youtube.com

Women who had their first period at or before the age of 11 are at increased risk for premature and early menopause and the risk is further amplified if the woman is nulliparous according to a large observational study published on January 25, 2017 in Oxford Journal of Human Reproduction.

It is already known that premature menopause and early menopause are at high risk for CHD, CVD and all-cause mortality. These women can be benefited by pharmacological and life style interventions to prevent the increased all-cause mortality and CVD risk they are put at due to accelerated reproductive aging.[1]

This was a pooled analysis of data of 51,450 postmenopausal women from observational studies that contributed to The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project.[2]

InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies.

Age at menarche was categorized into ≤11, 12, 13, 14 or more years and parity as nulliparous, 1 or 2 children. Premature Menopause is defined as Final Menstrual Period (FMP) before the age of 40 years and Early menopause is when FMP is between 40–44 years.

After multivariate regression analysis, it was seen that:

Median age at menopause was 50 years. About 2% of women had early menopause and nearly 8% women had premature menopause.

Women with first period at ≤11 years of age were 1.39 times the risk early menopause, 1.8 times the risk of premature menopause as compared to women who had first period after ≥12 years of age of age.  

Nulliparous women were at 1.32 times the risk of early menopause 2.26 times the risk of premature menopause.

Women who were nulliparous and had menarche at ≤11 years of age were 2 times the risk for early menopause and 5 times the risk for premature menopause as compared to those who had menarche ≥12 years and had one or more children.

The study supports the finding that women at risk of premature/early menopause can be identified  by history and can be  benefited by pharmacological and lifestyle interventions to prevent the increased all-cause mortality and CVD risk they are put at due to accelerated reproductive aging.

Complex relationship exists between cardiovascular health and accelerated reproductive aging and further research is needed to clarify the issue.

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[1] https://obgynupdated.blogspot.com/2016/09/premature-or-early-onset-menopause-is.html

[2] https://www.ncbi.nlm.nih.gov/pubmed/27621257

Premature or early onset menopause is associated with increased risk of CVD and all-cause mortality.

Clinical pearls:

• Women who had premature menopause are at high risk for CHD, CVD and all-cause mortality.
• With every 1 in 3 women dying due to CVD, identifying those who are high risks for it is important from public health perspective.
• Women with premature menopause can be benefited by pharmacological and life style interventions to prevent the increased all-cause mortality and CVD risk they are put at due to accelerated reproductive aging.

Majority of women around the world undergo menopause between 45 to 55 years of age with the average age being 51 years.[1] According to recent estimates about 5% of women attain natural menopause between the age of 41-45 years and additional 1% of have the last period before the age of 40.  Another 5% have premature menopause due to surgical removal of the ovaries, radiation and chemotherapy for malignancies or smoking.  The age at final menstrual period is of great public health significance and is considered as an important marker for predicting future cardiovascular, bone and overall health of the women. [2]

Women who attain menopause before 45 years of age have shorter total duration of estrogen exposure as compared to women who have menopause in 50s.

Multiple observational and cross sectional studies in the past have tried to assess the effect of loss of ovarian function and increased risk of cardiovascular diseases (CVD) and all-cause mortality in women undergoing premature menopause.

A recent meta-analysis published in JAMA cardiology by Muka et al [3] tried to systemically review and meta-analyze the relationship between age and duration of menopause and increased risk of cardiovascular diseases.

The analysis included 32 studies consisting of 310,329 non-overlapping women in their analysis.

The investigators compared the outcomes between women who entered menopause before 45 years of age to those women who were 45 or older at the onset. It was seen that women in the early menopause group had 1.5 times the risk of overall coronary heart disease, 1.11 times the risk of fatal coronary heart disease,1.23 times the risk for overall stroke, 0.99 for stroke mortality, 1.19 times the risk for CVD mortality, and 1.12 for all-cause mortality as compared to women who had menopause after the age of 45 years.

Women who had menopause between age of 50-54 have decreased risk (.87 times) of suffering from fatal CHD as compared to women who had menopause before 50 years of age. The risk for stroke was comparable in both the groups.

With every 1 in 3 women dying due to CVD, identifying those who are high risks for it might be important from public health perspective. Menopause might be a crucial period in women’s life to evaluate her future risk for CVD and introduce interventions to reduce the risk.

In an invited commentary about the article by Dr JoAnn E Manson (Harvard Medical School, Boston, MA) and D. Teresa K Woodruff (Northwestern University), the authors stress upon the complicated relationship between menopause and CVD. They discuss the findings of the Framingham Heart Study which states that increase in systolic, diastolic blood pressure, cholesterol and other vascular risk factors around pre and peri menopausal years led to an accelerated menopause at a younger age. The data from the study provides an important clue about cardiovascular health being responsible for menopausal timing, but it does not exclude a bidirectional relationship. [4]

An earlier Meta-analysis of observational study showed that bilateral surgical oophorectomy was associated with more than double the risk of CVD (risk ratio=2.62). Women who are put on HRT after the surgery nullify their increased risk for CVD as compared to women with intact ovaries.

A detailed analysis of Women’s Health Initiative study also stressed the beneficial effects of HRT in relation to cardiovascular health when initiated between the ages of 50 to 59 years as compared to older women. [5]

The ELITE: Early Versus Late Intervention Trial With Estradiol also affirms the timing hypothesis in relation to timing of estradiol administration, when a beneficial cardiovascular effect is only seen in women with early, but not later menopause. [6]

To conclude, the findings of the review indicates that women who had premature menopause are at high risk for CHD, CVD and all-cause mortality.

Complex relationship exists between cardiovascular health and accelerated reproductive aging and further research is needed to clarify the issue, but currently women with premature menopause can be benefited by pharmacological and life style interventions to prevent the increased all-cause mortality and CVD risk they are put at due to accelerated reproductive aging.

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[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285482/

[2] http://www.cdc.gov/reproductivehealth/infertility/

[3] http://cardiology.jamanetwork.com/article.aspx?articleid=2551981

[4] http://amaprod.silverchaircdn.com/data/Journals/CARDIOLOGY/0/hic160023.pdf.gif

[5] https://www.nhlbi.nih.gov/whi/

[6] https://clinicaltrials.gov/ct2/show/NCT00114517