Ovarian reserve and anti-Mullerian hormone (AMH) in mothers of dizygotic twins

This study aimed to explore if natural dizygotic (DZ) twinning is associated with earlier menopause and lower anti-Mullerian hormone (AMH) values. We investigated if advanced biological reproductive aging, which can be responsible for the multiple follicle growth in familial twinning, is similar to mechanisms that occur in normal ovarian aging, reflected by earlier menopause in mothers of DZ twins and lower levels of AMH. A total of 16 mothers of DZ twins enrolled with the Netherlands Twin Register (average age at first assessment: 35.9 +/- 3.0 years) and 14 control mothers (35.1 +/- 3 years) took part in a prospective study. Fifteen years after entry into the study, which included follicle-stimulating hormone (FSH) assessment, AMH was measured in stored serum samples and menopause status was evaluated. Average AMH levels were not significantly different between DZ twin mothers and controls (2.1 +/- 2.4 mu g/L vs. 1.9 +/- 1.9 mu g/L). Among the 16 mothers of twins, 7 had an elevated (FSH) value over 10 U/L at first assessment. Their AMH levels were lower than the nine twin mothers with normal FSH values: 0.6 +/- 0.4 versus 3.4 +/- 2.6 mu g/L (p = .01). Of the mothers of twins, eight mothers had entered menopause at the second assessment compared with only one control mother (p = .07). Thus, slightly more DZ mothers were in menopause than the control mothers, although this difference was not significant. The subgroup of DZ twin mothers who had an increased FSH concentration 15 years ago had a limited ovarian reserve as reflected by lower AMH levels. These data indicate that advanced ovarian aging can be a feature in familial DZ twinning, particularly with elevated early follicular phase FSH

Prevalence of Polycystic Ovary Syndrome in Women from Opposite-Sex Twin Pairs

Introduction: Intrauterine androgens of a male fetus may influence the female fetus in opposite-sex twin pairs. Because female intrauterine overexposure to androgens could lead to polycystic ovary syndrome (PCOS), the prevalence of PCOS should be higher in women from opposite-sex twin pairs. Therefore, the aim of the current study was to evaluate the prevalence of PCOS in women from opposite-sex twin pairs compared to women from same-sex twin pairs, sisters, and female spouses of twins. Subjects and Methods: Data from 1325 monozygotic twins, 1191 dizygotic twins (711 women from same-sex twin pairs and 480 women from opposite-sex twin pairs), 745 sisters of twins, and 218 spouses of male twins were evaluated. PCOS was defined as less than nine natural menstrual cycles a year combined with either hirsutism or acne. The prevalence of PCOS was compared using a ±2 test. Binary logistic regression analyses were conducted to test for confounding effects of smoking, age, and body mass index. Results: No significant differences in PCOS prevalence were found between women from same-sex twin pairs (either monozygotic or dizygotic), opposite-sex twin pairs, sisters, and spouses. Conclusion: The prevalence of PCOS is not different in women from opposite-sex and same-sex twin pairs, singleton sisters, or spouses. This indicates that possible androgen exposure of the female fetus, caused by a shared intrauterine environment with a male fetus, does not result in PCOS-like traits. Copyright © 2009 by The Endocrine Society

Heritability of Polycystic Ovary Syndrome in a Dutch Twin-family study

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. There is evidence for a genetic component in PCOS based on familial clustering of cases. Objective: In the present study, the heritability of PCOS was estimated. Design/Participants: Data from 1332 monozygotic twins (genetically identical) and 1873 dizygotic twins/singleton sisters of twins (who share on average 50% of their segregating genes) registered with The Netherlands Twin Register were used. PCOS was defined as less than nine menstrual cycles and acne or hirsutism in agreement with the 2003 Rotterdam consensus. Results: Results point to a strong contribution of familial factors to PCOS. The resemblance in monozygotic twin sisters (tetrachoric correlation 0.71) for PCOS was about twice as large as in dizygotic twin and other sisters (tetrachoric correlation 0.38). Univariate analyses point to strong contributions of genetic factors to the variance in PCOS. Next, a trivariate genetic analysis of oligomenorrhea, acne, and hirsutism was carried out. This analysis confirmed that the familial component in PCOS is due to genetic factors. Conclusions: This study demonstrated a large influence of genetic factors to the pathogenesis of PCOS, justifying the search for susceptibility genes. Copyright © 2006 by The Endocrine Society

Efficient sweet pepper transformation mediated by the BABY BOOM transcription factor

Pepper (Capsicum L.) is a nutritionally and economically important crop that is cultivated throughout the world as a vegetable, condiment, and food additive. Genetic transformation using Agrobacterium tumefaciens (agrobacterium) is a powerful biotechnology tool that could be used in pepper to develop community-based functional genomics resources and to introduce important agronomic traits. However, pepper is considered to be highly recalcitrant for agrobacterium-mediated transformation, and current transformation protocols are either inefficient, cumbersome or highly genotype dependent. The main bottleneck in pepper transformation is the inability to generate cells that are competent for both regeneration and transformation. Here, we report that ectopic expression of the Brassica napus BABY BOOM AP2/ERF transcription factor overcomes this bottleneck and can be used to efficiently regenerate transgenic plants from otherwise recalcitrant sweet pepper (C. annuum) varieties. Transient activation of BABY BOOM in the progeny plants induced prolific cell regeneration and was used to produce a large number of somatic embryos that could be converted readily to seedlings. The data highlight the utility of combining biotechnology and classical plant tissue culture approaches to develop an efficient transformation and regeneration system for a highly recalcitrant vegetable crop

Ovarian volume and antral follicle count for the prediction of low and hyper responders with in vitro fertilization

BACKGROUND: The current study was designed to compare antral follicle count (AFC) and basal ovarian volume (BOV), the exogenous FSH ovarian reserve test (EFORT) and the clomiphene citrate challenge test (CCCT), with respect to their ability to predict poor and hyper responders. METHODS: One hundred and ten regularly menstruating patients, aged 18–39 years, participated in this prospective study, randomized, by a computer designed 4-blocks system study into two groups. Fifty six patients underwent a CCCT, and 54 patients underwent an EFORT. All patients underwent a transvaginal sonography to measure the basal ovarian volume and count of basal antral follicle. In all patients, the test was followed by a standard IVF treatment. The result of ovarian hyperstimulation during IVF treatment, expressed by the total number of follicles, was used as gold standard. RESULTS: The best prediction of ovarian reserve (Y) was seen in a multiple regression prediction model that included, AFC, Inhibin B-increment in the EFORT and BOV simultaneously (Y = -3.161 + 0.805 × AFC (0.258-1.352) + 0.034 × Inh. B-incr. (0.007-0.601) + 0.511 BOV (0.480-0.974) (r = 0.848, p < 0.001). Univariate logistic regression showed that the best predictors for poor response were the CCCT (ROC-AUC = 0.87), the bFSH (ROC-AUC = 0.83) and the AFC (ROC-AUC = 0.83). Multiple logistic regression analysis did not produce a better model in terms of improving the prediction of poor response. For hyper response, univariate logistic regression showed that the best predictors were AFC (ROC-AUC = 0.92) and the inhibin B-increment in the EFORT (ROC-AUC = 0.92), but AFC had better test characteristics, namely a sensitivity of 82% and a specificity 89%. Multiple logistic regression analysis did not produce a better model in terms of predicting hyper response. CONCLUSION: In conclusion AFC performs well as a test for ovarian response being superior or at least similar to complex expensive and time consuming endocrine tests. It is therefore likely to be the test for general practise

Total fertilization failure and idiopathic subfertility

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Familial twinning and fertility in Dutch mothers of twins.

We studied twinning and fertility indices in mothers with spontaneous monozygotic (MZ) and dizygotic (DZ) twins and in mothers who conceived their twins after the use of assisted reproduction techniques (ART). Participants in this study consisted of 8,222 and 5,505 women with spontaneous DZ and MZ offspring and 4,164 and 250 women with ART DZ and MZ twin pairs, respectively. Women were compared with respect to the number of sibs and offspring, the presence of other relatives with twins and the time it took to conceive the twins. We also compared familial twinning between a younger and an older age group. Women with spontaneous DZ twins more often reported female relatives with twins than those with spontaneous MZ twins. The proportion of DZ versus MZ twin offspring in relatives was also larger in women with spontaneous DZ offspring than in women with MZ offspring. The first group of women reported a shorter time to conceive. Women with ART twins had fewer sibs and offspring and less often reported relatives with twins. We did not observe that DZ twinning was more familial in women who had their twins before age 36 years compared to older women. Familial DZ twinning is clearly present in mothers of spontaneous DZ twins. The mechanisms underlying spontaneous and non-spontaneous DZ twinning are different and fertility treatment should be taken into account in any study of twinning. Twinning is not more familial in women who have their twins at a younger age

Increased levels and pulsatility of Follicle-Stimulating Hormone in mothers of hereditary dizygotic twins

According to the endocrine model of hereditary dizygotic twinning, high FSH is responsible for multiple ovulation and pregnancy. Our study explored the underlying neuroendocrine causes

Heritability of reproductive hormones in adult male twins

Background: Proper functioning of the male reproductive axis depends on complex feedback systems between several hormones. In this study, the genetic contribution of various endocrine components of the hypothalamic-pituitary-testicular axis is evaluated and previously observed differences in FSH and inhibin B levels between mono- (MZ) and dizygotic (DZ) twins are re-investigated. Methods: Inhibin B, FSH, LH, sex hormone-binding globulin (SHBG) and testosterone levels were assayed in 128 adult males (20 MZ twin pairs, 7 single MZ twins, 10 DZ twin pairs, 27 single DZ twins and 34 siblings of twins, constituting 10 sibling pairs), aged 15.6-68.7 years. Hormone levels were compared across zygosity groups and heritability estimates were obtained using maximum likelihood variance component analysis. Results: Heritability estimates ranged from 56% (testosterone) to 81% (inhibin B and SHBG). For LH and FSH, the heritability was estimated at 68% and 80% respectively. No mean differences in hormone levels were observed across groups. Conclusions: All measured hormones are highly heritable. A difference in the FSH-inhibin B feedback system between DZ twin males and MZ twin males could not be confirmed. © The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved