Serum anti-Mullerian hormone levels are negatively related to Follicular Output RaTe (FORT) in normo-cycling women undergoing controlled ovarian hyperstimulation

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V.K. Genro1,2,3,4, M. Grynberg1,2,3, J.B. Scheffer1,2,3, I. Roux1,2,3, R. Frydman1,2,3 and R. Fanchin1,2,3,*

1Service de Gynécologie-Obstétrique et Médecine de la Reproduction, AP-HP, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, Clamart F-92141, France

2Univ Paris-Sud, Clamart F-92140, France

3INSERM, U782, Clamart F-92140, France

4Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Porto Alegre, Brazil *Correspondence address. Tel: +33-1-45-37-40-53; Fax: +33-1-45-37-49-80; E-mail: renato.fanchin{at}abc.ap-hop-paris.frReceived August 25, 2010. Revision received November 9, 2010. Accepted November 24, 2010. BACKGROUND Since in rodents anti-Müllerian hormone (AMH) has been shown to inhibit antral follicle responsiveness to FSH, we aimed at verifying whether a relationship exists between serum AMH levels and antral follicle responsiveness to exogenous FSH in normo-cycling women.

METHODS Serum AMH, estradiol (E2) and FSH levels were prospectively measured on cycle day 3 in patients undergoing controlled ovarian hyperstimulation (COH) with a time-release GnRH agonist and standardized FSH doses. In 162 patients, follicles were counted after pituitary suppression and before FSH administration (baseline; small antral follicles; 3–8 mm), and on the day of hCG (dhCG; pre-ovulatory follicles; 16–22 mm). Antral follicle responsiveness to FSH was estimated by the Follicular Output RaTe (FORT), determined by the ratio pre-ovulatory follicle count on dhCG × 100/small antral follicle count at baseline.

RESULTS Serum AMH levels were positively correlated with the number of small antral follicles at baseline (r = 0.59; P < 0.0001) and pre-ovulatory follicles on dhCG (r = 0.17; P < 0.04). Overall, FORT was 47.5 ± 1.4% and failed to be influenced by the woman's age, BMI or basal E2 and FSH level. Conversely, multiple regression analysis showed that FORT was negatively correlated with AMH levels (r = -0.30; P < 0.001), irrespective of duration of COH and total FSH dose.

CONCLUSIONS The percentage of follicles that effectively respond to FSH by reaching pre-ovulatory maturation is negatively and independently related to serum AMH levels. Although the mechanisms underlying this finding remain unclear, it is in keeping with the hypothesis that AMH inhibits follicle sensitivity to FSH.

© The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (3): 671-677. doi: 10.1093/humrep/deq361 First published online: December 21, 2010

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Clinical grade vitrification of human ovarian tissue: an ultrastructural analysis of follicles and stroma in vitrified tissue

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Mona Sheikhi1,*, Kjell Hultenby2, Boel Niklasson1, Monalill Lundqvist1 and Outi Hovatta1

1Division of Obstetrics and Gynaecology, Department of Clinical, Science, Technology and Intervention, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

2Division of Clinical Research Centre, Department of Laboratory Medicine, Karolinska Institutet, SE 141 86 Stockholm, Sweden *Correspondence address. Tel: +46-8-5858-0000; Fax: +46-8-58587250; E-mail: mona.sheikhi{at}karolinska.seReceived March 17, 2010. Revision received November 10, 2010. Accepted November 22, 2010. BACKGROUND Cancer therapy is one of many conditions which may diminish the ovarian reserve. Banking of human ovarian tissue has become an option for the preservation of female fertility. We have shown that vitrification is an excellent method to cryopreserve ovarian tissue. To carry out vitrification in a clinical setting, we have developed a clinical grade closed system to avoid direct contact of ovarian tissue with liquid nitrogen.

METHODS Ovarian tissue was obtained by biopsy from 12 consenting women undergoing Caesarean section. Tissues were vitrified in cryotubes, using dimethyl sulphoxide, 1,2-propanediol, ethylene glycol and polyvinylpyrrolidon as cryoprotectants. Non-vitrified and warmed-vitrified tissue was compared by light and electron microscopic morphology of the follicles within the tissues.

RESULTS We did not see any differences in the light or electron microscopic ultrastructure of oocytes between non-vitrified and vitrified tissues. No irreversible subcellular alterations in vitrified tissues were seen.

CONCLUSIONS The ultrastructure of follicles within the vitrified human ovarian tissue was well preserved using cryotube in a closed vitrification system to avoid direct contact of liquid nitrogen. The system is compatible with the European tissue directive.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

This ArticleHum. Reprod. (2011) 26 (3): 594-603. doi: 10.1093/humrep/deq357 First published online: January 8, 2011

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Reply: In situ identification of follicles in ovarian cortex as a tool for quantifying follicle density, viability and developmental potential in strategies to preserve female fertility

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Haplotype analysis of chemokine CXCL12 polymorphisms and susceptibility to premature ovarian failure in Chinese women

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Binbin Wang1,2,†, Peisu Suo1,2,†, Beili Chen3, Zhaolian Wei2, Lu Yang3, Sirui Zhou1,2, Jing Wang1,2, Yunxia Cao3 and Xu Ma1,2,4,*

1Center for Genetics, National Research Institute for Family Planning, 12, Dahuisi Road, Haidian, Beijing 100081, China

2Peking Union Medical College, Beijing, China

3Reproductive Medicine Center, First Affiliated Hospital, Anhui Medical University, Hefei, China

4World Health Organization Collaborating Centre for Research in Human Reproduction, Beijing, China *Correspondence address. Tel: +86-10-62176870; Fax: +86-10-62179151; E-mail: genetic{at}263.net.cn?† These authors contributed equally to the work.

Received June 5, 2010. Revision received December 19, 2010. Accepted January 5, 2011. BACKGROUND Chemokine (C-X-C motif) ligand 12 (CXCL12/stromal cell-derived factor 1) has been suggested to play an essential role in primordial germ cell migration, colonization and survival, and in the primordial to primary follicle transition. This study was performed to investigate an association of polymorphisms in CXCL12 with the risk of premature ovarian failure (POF) in Chinese patients.

METHODS Tagging single nucleotide polymorphisms (SNPs) were selected using the Chinese HapMap database. Five SNPs (rs4948878, rs1801157, rs266087, rs266093 and rs1029153) were genotyped by direct sequencing in 111 patients with POF and 183 healthy controls recruited from the First Affiliated Hospital, Anhui Medical University, China.

RESULTS Compared with controls, there were significantly higher frequencies of the rs1801157 A allele and haplotype C-T-A-T-T in cases with POF [P = 6.38E-07, odds ratio (OR) = 3.10, 95% confidence interval (CI) 1.955–4.890 by allele; P = 7.0E-04, OR = 2.39, 95% CI 1.43–3.97 by haplotype]. No differences were observed for the other four SNPs between POF cases and controls.

CONCLUSIONS A strong association between a CXCL12 polymorphism and POF was established in Chinese patients, suggesting that CXCL12 might be a new candidate gene involved in POF. The A allele of CXCL12 polymorphism rs1801157 is a possible risk factor for developing POF. However, further independent studies are necessary to confirm our findings.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 950-954. doi: 10.1093/humrep/der001 First published online: February 4, 2011

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

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