Intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency.

OBJECTIVE: To compare the prevalence of intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency (oPOI) and in controls. DESIGN: Observational study. SETTING: Division of Infertility and Service of Genetic Medicine, Geneva University Hospitals. PATIENT(S): The study group consisted of 27 infertile women with oPOI referred by infertility specialists for FMR1 testing in 2005-6 because of unexplained poor response to controlled ovarian hyperstimulation or altered hormonal profiles. The control group consisted of 32 women undergoing genetic testing for conditions unrelated to mental retardation or ovarian function. The DNA samples were anonymized. INTERVENTION(S): In the study group, data were collected concerning reproductive/family history, hormonal markers, possible fertility treatment outcomes, and results of karyotype and FMR1 testing. In the control group, FMR1 gene testing was done. The only clinical data available in controls were sex and indication for genetic testing. MAIN OUTCOME MEASURE(S): Distribution of FMR1 alleles. RESULT(S): Six (22%) of 27 women with oPOI had FMR1 alleles of >40 repeats (intermediate to premutation range), compared with one (3%) of 32 controls. CONCLUSION(S): These results suggest that women with oPOI might be at risk of carrying alleles in the intermediate and premutation range.

Clinical uses of anti-Müllerian hormone assays: pitfalls and promises.

OBJECTIVE: To investigate whether the controversy about fluctuations of anti-Müllerian hormone (AMH) levels during the menstrual cycle results from differences between the immunoassays currently available: the Beckman Coulter Immunotech kit (Fullerton, CA) and the Diagnostic Systems Laboratories kit (Webster, TX). DESIGN: Prospective trial. SETTING: Fertility clinics of two tertiary university hospitals. PATIENT(S): One hundred sixty-eight blood samples from three different populations. Serial samples at set intervals from the LH surge were taken in a fourth population of 10 volunteers. INTERVENTION(S): We remeasured AMH levels by using the Diagnostic Systems Laboratories kit in 168 blood samples in which AMH initially had been measured by using the Beckman Coulter assay. We also conducted serial AMH measurements (n = 7) during the menstrual cycle of 10 women. MAIN OUTCOME MEASURE(S): Linear regression of AMH levels determined by using 2 different assays and analysis of variance of serial measurements in the menstrual cycle. RESULT(S): We found a linear relationship between the 2 methods, with a correlation coefficient of 0.88. When repeated individual AMH measures were longitudinally analyzed in relation to the LH surge, a slight but significant decrease was observed after ovulation. CONCLUSION(S): Differences in AMH fluctuations during the menstrual cycle reported in recent publications do not result from the use of different AMH assays. The changes in AMH levels after ovulation are slight, yet statistically significant. However, the fluctuations observed are smaller than intercycle variability and therefore are not clinically relevant as far as AMH measurements for clinical purposes are concerned. In daily practice, AMH therefore can be measured anytime during the menstrual cycle.

[Preservation of women fertility facing potential premature ovarian failure]. / Stratégies de préservation de la fertilité en cas de risque d'insuffisance ovarienne précoce.

Numerous pathologies and their treatments may alter ovarian reserve in women and girls and may harm their future fertility. Oocytes cryopreservation techniques may be used in a limited number of cases, excluding young patients. We hereby report results obtained with our and other teams' ovarian tissue vitrification techniques. This new approach can be offered to young patients before puberty and should not delay both chemotherapy and radiotherapy when needed. Major drawbacks include potential alteration of ovarian reserve, as well as recurrence of the original malignancy. The later can be circumvented using in vitro maturation techniques. It is important to discuss fertility preservation opportunities with every woman or girls facing potential premature ovarian failure.

Undetectable serum anti-Müllerian hormone levels and occurrence of ongoing pregnancy.

OBJECTIVE: To discuss, on the basis of the experience of two clinical cases and extensive literature review, the significance of extremely low levels of anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting substance, in infertile women. DESIGN: Case report. SETTING: University-based infertility clinic at a medical center in Switzerland. PATIENT(S): Two women, 29 and 41 years of age and with a 2- and 4-year history of secondary infertility, respectively. INTERVENTION(S): Clinical, radiological, and biological investigation of infertility, including repeated measurements of the serum AMH with serial ELISA assays. MAIN OUTCOME MEASURE(S): Levels of AMH and development of ongoing pregnancy. RESULT(S): Both women had a spontaneous ongoing pregnancy despite undetectable AMH levels. CONCLUSION(S): Although it is helpful for day-to-day management of infertile patients, the predictive value of AMH for the occurrence of a spontaneous ongoing pregnancy has limits.

Serum antimüllerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids.

OBJECTIVE: To investigate whether oral or vaginal administration of contraceptive hormones might affect antimüllerian hormone (AMH) levels. DESIGN: Prospective trial with women recruited by advertisement. Women who wished contraception were randomized between oral or vaginal estroprogestative contraception, and those who did not choose contraception were included in the control group. SETTING: Fertility clinic of a tertiary university hospital. PATIENT(S): Twenty-four young, healthy volunteer women with regular cycles who had received no hormonal contraception for at least 3 months before the study. INTERVENTION(S): Oral or vaginal estroprogestative contraception from day 5 to 25 of a menstrual cycle versus no contraception. MAIN OUTCOME MEASURE(S): Intercycle and intracycle variations of serum AMH levels in normally ovulating volunteers and following the initiation of oral or vaginal estroprogestative contraception. RESULT(S): Fluctuations of AMH levels observed during the menstrual cycle remained within cycle-to-cycle variability in cycling controls and in women receiving oral or vaginal contraception. CONCLUSION(S): Our findings confirm that AMH levels remain steady during the menstrual cycle and indicate that they are unaffected by exogenous sex steroids used for contraception whether administered orally or vaginally.

Outlook: Roles of FSH and LH during the follicular phase: insight into natural cycle IVF.

A mounting interest in natural cycle IVF has challenged the medical community to better understand the mechanisms controlling the follicular phase and ovulation in particular, in an effort to optimize this procedure and its outcome. For practical reasons, the advancement of the follicular phase in the menstrual cycle is commonly timed according to the onset of last menses. However, this precludes knowing when the follicular phase truly begins and hampers the possibility of optimizing timing of late follicular-phase events, notably, the triggering of ovulation. Clinicians, therefore, use surrogate markers of follicular maturation, such as oestrogen production and follicular size. Because it is impossible to identify the low-amplitude intercycle basal FSH signal, efforts have reverted toward controlling when it takes place, either with exogenous oestrogen or with oral contraceptives. In the late follicular phase, the occurrence of LH surge results from a balance between the opposite effects of rising oestrogen concentrations, which favour the LH surge, and the opposing effects mediated by the gonadotrophin surge-attenuating factor, a peptide of ovarian origin. This review looks into the mechanisms that control these two hinges of the follicular phase, the basal FSH signal and LH surge, in the context of optimizing natural cycle IVF.