Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Archana Dambal

"Journal of clinical and diagnostic research is a welcome change in publishing practices. It aims to reach out to the grass-root level researchers who do not lack in experience, clinical material and ideas, but lack in their knowledge in English language and statistics. The journal achieves it's aim by supporting in these exact domains.
It also gives due credit to all research designs like descriptive and qualitative studies while many journals ignore these important study designs. The rigorous review process does not allow any compromise in quality
It is indexed in many indexing agencies and the articles are available under creative commons licence free of cost
The frequency of publication supports many aspiring authors from India and other countries.
It's wide scope welcomes articles across various specialities in medicine. In an era when there is an unscientific insistence on speciality specific research by regulatory bodies in medical education, JCDR supports collaborative research across specialities. I wish the publisher all the best in his future endeavors."



Dr. Archana Dambal
Department of General Medicine,
Belgaum Institute of Medical Sciences,Belgaum, Karnataka,INDIA,
On 30 Nov 2018




Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Reviews
Year : 2011 | Month : April | Volume : 5 | Issue : 2 | Page : 384 - 387

The Role of the Anti-Müllerian Hormone in Female Fertility: A Review

PRIYA DAHIYA, KIRAN DAHIYA, RAKESH DHANKHAR, NAVDEEP HOODA, K.D. NAYAR

Dept of Infertility & IVF, Akanksha IVF Center, Mata Chanan Devi Hospital, Janak Puri, New Delhi, India. Dept of Biochemistry Pt. B.D.Sharma PGIMS, Rohtak, Haryana, India. Dept of Radiotherapy, Pt. B.D.Sharma PGIMS, Rohtak, Haryana, India. Spectrum Imaging & Diagnostic Centre, Paschim Vihar, New Delhi, India.

Correspondence Address :
Kiran Dahiya, 778/28, Bharat Colony, Rohtak, Haryana, India.
PIN: 124001
Email: kirandahiya_2002@yahoo.com, Phone: +91 9896111985

Abstract

The Anti- Müllerian hormone (AMH) is a recent biomarker for the ovarian reserve. Initially, it was considered mainly in the context of the müllerian regression and the sexual differentiation in males, but its role in ovarian functions is gaining interest very fast. It is mainly expressed in the small antral follicles and its levels decline with the growth in the follicular size. Its capability as a predictor for ovarian response can be utilised to devise a more individualised approach in the patients who opt for assisted reproductive technology (ART). It has an inhibitory effect on the primordial follicular recruitment in the ovary and on the responsiveness of the growing follicles to the follicle stimulating hormone (FSH); thus it is important in patients with polycystic ovary syndrome. This review summarizes the recent findings which concern AMH and its role in the female fertility.

Keywords

Anti- Müllerian hormone, ovarian reserve, ovarian response, female fertility

How to cite this article :

PRIYA DAHIYA, KIRAN DAHIYA, RAKESH DHANKHAR, NAVDEEP HOODA, K.D. NAYAR. THE ROLE OF THE ANTI-MÜLLERIAN HORMONE IN FEMALE FERTILITY: A REVIEW. Journal of Clinical and Diagnostic Research [serial online] 2011 April [cited: 2019 Feb 16 ]; 5:384-387. Available from
http://www.jcdr.net/back_issues.asp?issn=0973-709x&year=2011&month=April&volume=5&issue=2&page=384-387&id=1261

The Anti- Müllerian hormone (AMH), which is also known as Müllerian- inhibiting substance (MIS), is a member of the transforming growth factor-beta (TGF-β) superfamily, which includes more than 35 structurally related peptides, including activins, inhibins, bone morphogenic proteins (BMPs) and growth differentiation factors. Many of these are involved in the reproductive function of both the sexes (1), (2). AMH is a homodimeric, disulfide-linked glycoprotein with a molecular weight of 140 kDa. Its gene is located on the short arm of chromosome 19, band 19p 13•3.2 in humans. The AMH gene is 2750 bps long and it is divided into five exons (3), (4). AMH is strongly expressed in the Sertoli cells from testicular differentiation upto puberty and to a much lesser degree in the granulosa cells (GCs) also. It is responsible for the ipsilateral regression of the müllerian duct by eight weeks. After the involution of the müllerian system, AMH continues to be secreted, but it has no known function. Although it may have no role in the female development, its production later in life by the granulosa cells raises the possibility of autocrine and paracrine actions in oocyte maturation and follicle development (3)(4)(5)

Mechanism of Action:
The members of the TGF-β superfamily exert their effects through the serine/threonine kinase receptors. AMH acts on its own specific type II receptor, AMHR2 to signal through a BMP-like pathway, by recruiting one of the type I receptors; ALK 2, 3 or 6 (6), (7). The downstream signalling of the AMH receptor involves cytoplasmic effectors which are known as receptor-related SMAD proteins (RSmads 1, 5 and 8) and a common SMAD4 protein. Once AMH binds to AMHR2, the type I receptor becomes recruited, thus forming a receptor complex. This results in the activation of the type I receptor, which causes the phosphorylation of the R-Smads. These proteins bind to the common SMAD4 protein, resulting in the translocation of the complex into the nucleus and its binding directly to the DNA to regulate gene expression or interacting with other DNA-binding proteins (8), (9). In humans, the mutations of either the AMH or the AMHR2 gene are the causes of the persistent müllerian duct syndrome (7)(8)(9)(10)(11).

The expression of AMH in the ovary:
Ovarian AMH has been reported to be produced from 36 weeks of gestation in the GCs and to be expressed until menopause. The AMH expression in rats, mice, sheep and q 2010 human ovaries has been demonstrated by using in situ hybridisation or immunostainingWhen AMH expression begins precisely during folliculogenesis is still unclear, with the studies on the primordial follicles producing equivocal results, but it is clear that the highest expression of AMH is found in the preantral and the small antral follicles, the latter being those which are involved in the follicle stimulating hormone (FSH)- dependent cyclic recruitment (12), (13). After selection, the level of expression gradually declines in the mural GCs, with the AMHpositive staining becoming localized to the cumulus GCs. Direct measurements of the AMH protein production by the human GCs and the follicular fluid confirmed that the highest concentrations were in the small antral follicles and that they became very low or undetectable in the larger ones (14). The cessation of production of AMH from these follicles suggests that this is an important requirement for the selection of the dominant follicle. Neither AMH staining nor AMH mRNA expression was observed in the oocytes, the corpus luteum, the atretic follicles or the theca cells in mice, rats or human ovaries, thus confirming that the GCs are the only sources of AMH in the ovary (11)(12)(13)(14)(15)

The function of AMH in the normal ovary:
The role of AMH in the normal ovarian function has been demonstrated with the help of AMH knockout (AMHKO) mice. These were found to be fertile, but had an increase in the number of growing follicles, thus resulting in the depletion of the primordial pool and the early cessation of ovulation, effects which were reversed by the culture of the ovaries from 2-day-old mice with AMH. These results were confirmed by the culture of mouse AMHR2-null or wild-type ovaries beneath the chorioallantoic membrane of chick embryos (‘in ovo’). In this position, the pieces of tissue become vascularised, thereby preventing the normal loss of the follicles which occurs in culture (16), (17). There was an increase in the follicle growth when compared to the wild-type, in those pieces which lacked the AMH receptor. In the human tissue, the picture was rather less straightforward. In cultured human ovarian cortical biopsies, AMH treatment (100 ng/ml) reduced the primordial follicle growth as compared to the untreated tissue, while a higher dose of AMH actually increased the numbers of the growing primordial follicles (18), (19). In the antral follicles, the overall effect of AMH reduced the sensitivity of the follicles to FSH, as suggested by a number of in vitro studies. In rat GCs, the FSH- and cyclic adenosine monophosphate (cAMP)-stimulated aromatase activity was significantly reduced after the AMH treatment. It has also been reported that AMH reduced the aromatase mRNA expression in the cAMP stimulated cells andreduced the luteinizing hormone (LH) receptor mRNA expression in porcine GCs which were stimulated with FSH (20). Even in the low FSH environment of the AMHKO mouse, there was an increase in the number of growing follicles as compared to the wild-type littermates. An inhibitory effect of AMH on the FSH-stimulated aromatase mRNA expression and estradiol production has also been shown in human GCs (21), (22).

Thus, AMH performs an inhibitory role in the antral follicle growth, and it can be envisioned that high concentrations of AMH in the small antral follicles would hold back the FSH responsiveness and steroidogenesis and the acquisition of the LH receptors until the time of follicle selection. By the time the intercycle rise in the FSH would occur, the AMH production would cease, the concentrations would fall and the follicle would be ‘released’ to produce estradiol. However, the factors which cause the inhibition of AMH production in these selected follicles remain unknown, but the identification of this inhibitor is important, as it may provide a clue as to why the AMH production is high in polycystic ovarian syndrome (PCOS) (18), (23), (24).

There is one other important question which arises, regarding the role of AMH in these small follicles. It is well described that AMH causes the regression of the müllerian duct by inducing cellular apoptosis (25). It is therefore interesting to speculate as to why the high concentrations in the small follicles are not similarly damaging. In the müllerian duct, atresia occurs in a pattern from cranial to caudal following the AMHR2 gradient, but why these follicles do not similarly undergo atresia due to cellular apoptosis, is not clear as yet. It may be that the ovarian cells lack the requisite intermediary pathways for this process, but no such report is still available. Therefore, the research into the role of ovarian AMH and the expression pattern of the receptor clearly needs to address this issue, taking into account the high concentrations which are found in PCOS.

Ovarian reserve and Fertility:
Ovarian reserve (OR) is a measure of the number and the quality of the eggs which are remaining in the woman’s ovaries - as well as the ability of the ovaries to respond to injectable FSH stimulation. A patient’s OR determines the prognostic chances of the fertility treatments and her treatment options. The best possible assessments of OR, therefore represent a core issue in modern infertility care. Various methodologies have been applied to maximize the accuracy of the OR determinations, though none have been universally accepted as superior to others. The follicle stimulating hormone (FSH) is still considered as the most widely utilized tool in routine daily practice, though the antral follicle counts and AMH have increasingly gained popularity (26), (27).

Research shows that the size of the pool of the growing follicles is heavily influenced by the size of the pool of the remaining primordial follicles (microscopic follicles in “deep sleep”). Therefore, the AMH blood levels have been thought to reflect the size of the remaining egg supply or the ovarian reserve. With the increasing ages of the females, s the size of their pool of remaining microscopic follicles decreases. Likewise, their blood AMH levels and the number of ovarian antral follicles which are visible by ultrasound also decrease (27). Women with many small follicles such as those with polycystic ovaries, have high AMH hormone values and women who have a few remaining follicles and those who are close to menopause, have low AMH levels (28), (29).

AMH levels and Conception:
Serum AMH levels in women are lower than those in men throughout life25. One potential advantage of using an AMH test as a marker of OR, is that it does not seem to change over the course of the menstrual cycle; FSH, on the other hand, must be measured on day 2 or day 3 of the menstrual cycle or on day 10 if it is drawn as a part of a clomid challenge test (CCT). Another point which is in favour of using it as a marker of OR is that AMH decreaseswith age (30), (31). Some studies in in vitro fertilization (IVF) patients have shown lower AMH levels in women who responded poorly to fertility drugs [32-34]. A correlation was found between the number of eggs which were retrieved and the AMH levels. The women with low AMH levels tended to get fewer eggs during IVF than the women with high AMH levels. Pregnancy rates were also lower in the women with low AMH levels (35)(36)(37)(38).

The interpretation of the AMH hormone levels is also subject to variation, as the levels which are considered to be “normal”, are still not clarified and agreed on by the experts. Also, different current commercial assays do not give equivalent results. Generally, the levels between 1-3 ng/ml are considered to be normal, 0.7-0.9 ng/ml to be low normal, 0.3-0.6 ng/ml to be low and less than 0.3 to be very low. The levelsabove 3.0 ng/ml are considered to be high and these may be associated with PCOS. But, there is a large subjective variation in the clinical interpretation (38)(39)(40).

AMH vs. other hormones as the predictors of conception:
The prediction of high ovarian response is still a great challenge in ART. There is a trend towards an individualised treatment to decrease complications, patient discomfort and cost in modern ART and it is necessary to identify the patients who are at a risk of the ovarian hyperstimulation syndrome and to use modified strategies for the stimulation, such as a gonadotropin –releasing hormone (GnRH)-antagonist regimen and mild stimulation protocols (41)(42)(43). Numerous studies have reported that the basal serum levels of AMH or inhibin B are good predictors of the ovarian response in patients who undergo ovarian hyperstimulation and in vitro fertilization (IVF) (44). Several reports also indicate that the basal serum levels of AMH are more discriminatory markers of the ovarian response than the basal follicle stimulating hormone (FSH), inhibin B, or oestradiol (45).

However, there were few reports which addressed the clinical significance of AMH and/or the inhibin B levels which were measured at the late follicular phase during the ovarian hyperstimulation.

Serum and follicular AMH levels at the time of the oocyte retrieval are positively correlated with the number of mature follicles and oocytes which are retrieved (46). A recent report indicated that the serum AMH values at the time of the human chorionic gonadotropin (hCG) administration are also correlated significantly with the number of the mature follicles, the number of oocytes which are retrieved and the serum oestradiol levels. Moreover, the AMH levels are correlated significantly with a greater number of 6-cell embryos and with better embryo morphology scores (47)(48)(49).

The serum inhibin B levels on the ovulation triggering day and the levels in the follicular fluids at the time of the oocyte retrieval are strongly correlated with the number of oocytes which are retrieved. The serum and follicular fluid levels of inhibin B at the ovum pick up are also correlated positively with the number of oocytes which are collected and are predictive of a clinical pregnancy. The serum inhibin B levels which are measured around the late follicular phase during the ovarian hyperstimulation can predict the number of oocytes which are retrieved, both in normal and poor responders (44). Since AMH is secreted mainly in the preantral and in the early small antral follicles, the circulating AMH level decreases through the maturing follicles in the normal menstrual cycle, and further decreases in the FSH-treated cycles (16), (27). In ovarian hyperstimulation and IVF cycles, however, the continued recruitment of the additional antral follicles during the stimulatory phase results in higher AMH levels and thus, it may be related to the number of mature follicles and the number of oocytes which are retrieved [49-51].

In contrast to AMH, inhibin B rises from the early follicular phase to reach a peak during the mid-follicular phase, but it continues to increase during the ovarian hyperstimulation. This suggests that inhibin B is secreted by the developing cohort of the antral follicles (44).

The follicular pool at the late follicular phase encompasses various stages of follicular development during the ovarian hyperstimulation. Therefore, the AMH and the inhibin B levels at the late follicular phase could reflect the overall ovarian pool, including the small and large antral and mature follicles (38). However, the follicular AMH levels were reported to be three times higher in the small follicles (<12 mm) than in the large follicles (>16 mm) and the serum AMH levels were tightly correlated with the follicular levels (50), (51). These findings suggest that the serum AMH levels may reflect the small antral follicular pool more and thus we postulated that the serum AMH levels on the ovulation triggering day can be related to the number of immature oocytes which are obtained. The FSH levels, for example, may vary with the day of the menstrual cycle and may be affected by other hormone levels. A patient with an elevated oestrogen level, for instance, may have an inaccurately low FSH level. This may lead to the false assumption of normal ovarian reserves (47)(52). The only problem with the estimation of the AMH levels is the cost. Its test is quite expensive as compared to the assays of other hormones. This fact may decrease its popularity in the developing countries as a routine test (53). But with the advent of modern biochemical techniques, there is hope for a more costeffective method for this test.

Conclusion

As compared to the other ovarian tests, AMH is a much better marker for the ovarian reserve. It is more stable than FSH and does not vary from cycle to cycle. It can be measured on any day of the cycle and so, it is preferred by many fertility specialists now-a-days. It has been demonstrated to be an accurate predictor of the ovarian response in controlled ovarian hyperstimulation in ART cycles, which may result in an optimized treatment burden, in a minimization of the risk of the ovarian hyperstimulation syndrome and in increased cost-effectiveness. Increased serum AMH levels have been found in women who are affected by PCOS, thus suggesting that the serum AMH levels may also be used in the diagnosis of PCOS. The ability of AMH to inhibit the growth of the tissues which are derived from the müllerian ducts, has raised hopes about its usefulness in the treatment of a variety of medical conditions including endometriosis, adenomyosis, and uterine cancer. Research on this is underway in several laboratories.

The major problem with the measurement of the AMH levels is the cost and that only few laboratories offer this test, especially in the developing countries. But reliable test kits from trusted brands are available now-a –days and big reputed laboratories are providing this facility. If the cost of the AMH measurement is compared to that of the reproductive hormone profile (which generally includes the levels of FSH, LH and prolactin), the difference is not much. So, the affordability is comparable. The establishment of a more economical method for this test will lead to an increase in its popularity and its use in the general population. The cost will also come down with an increase in its popularity. There seems to be little doubt on the fact that the research on AMH will continue in the years to come. A clearer understanding of its role in the ovarian physiology may help the clinicians to find a role for AMH measurement in the field of reproductive medicine by including it in the standard diagnostic procedures. It would seem that serum. There are other important factors that have to be taken into account while predicting the capability of a female in getting pregnant– lifestyle, infection, genetic abnormality, the quality of sperm and other male factors – but still, AMH is considered as the best hormone till date, to identify her potential reproductive capacity.

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