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

Users Online : 15399

AbstractMaterial and MethodsResultsDiscussionConclusionReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

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 Dermatolgy,
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
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : November | Volume : 16 | Issue : 11 | Page : BC01 - BC04 Full Version

Association between Thyroid Function and Ovarian Reserve in Infertile Women: A Cross-sectional Study


Published: November 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/58517.17085
Sandeep Singh Soam, Sonali Chaturvedi, Shruti Singh

1. Associate Professor, Department of Biochemistry, Government Medical College, Badaun, Uttar Pradesh, India. 2. Assistant Professor, Department of Biochemistry, Autonomous State Medical College, Mirzapur, Uttar Pradesh, India. 3. Senior Resident, Department of Community Medicine, Autonomous State Medical College, Mirzapur, Uttar Pradesh, India.

Correspondence Address :
Sandeep Singh Soam,
Santosh Bhawan, House No. 158, Bannu Miyan Colony, Rohta Road, Meerut, Uttar Pradesh, India.
E-mail: 1982shravansoam@gmail.com

Abstract

Introduction: Thyroid dysfunctions are among the most common diseases in women of reproductive age group. Thyroid hormone receptors are present on oocytes which indicate that thyroid hormones may influence ovarian functions. Serum Anti-Müllerian Hormone (AMH) is secreted from growing granulosa cells of ovaries. Serum AMH concentrations are used to evaluate ovarian reserve in females.

Aim: To find the association between ovarian reserve, measured by AMH concentration and thyroid functions in women with infertility.

Materials and Methods: This cross-sectional study was conducted on a total of 78 infertile females, in Department of Biochemistry at Government Medical College, Badaun, Uttar Pradesh, India, from July 2021 to December 2021. The involved women with infertility in the age group of 20-40 years attending the infertility clinic, were included in the study. Participants were divided into two groups based on whether the serum AMH value was <1 ng/mL (lower than low normal ovarian reserve) or ≥1 ng/mL (low normal to normal ovarian reserve). The blood samples were processed for Serum Thyroid Stimulating Hormone (TSH), free Triiodothyronine (fT3), free Thyroxine (fT4), Prolactin and AMH. The median values of TSH and fT4 levels were compared in the subgroups of patients defined by the level of serum AMH i.e., serum AMH value <1 ng/mL, and serum AMH value ≥1 ng/mL. Chi-square test was used to establish the association between the categorical variables.

Results: Based on serum AMH values, 22 (28%) females had below normal ovarian reserve i.e., serum AMH value <1 ng/mL, and 56 (72%) females had low normal to normal ovarian reserve i.e., serum AMH value ≥1 ng/mL. The mean age of participants with AMH <1 ng/mL was 33.23±4.28, which was significantly higher than those with AMH value ≥1 ng/mL (p-value=0.002). Serum TSH value was significantly higher in the subgroup of participants with AMH <1 ng/mL, the value being 4.75 mIU/L and was lower (2.8 mIU/L) in the subgroup of participants with AMH ≥1 ng/mL (p-value=0.002).

Conclusion: In conclusion, the present study found the highly significant difference in serum TSH values in the two groups based on whether the serum AMH value was <1 ng/mL and ≥1 ng/mL suggesting that subclinical hypothyroidism has negative impact on the female fertility. Increasing age of the females was negatively correlated with the ovarian reserve.

Keywords

Anti-müllerian hormone, Free thyroxine, Hypothyroidism, Reproductive age, Thyroid stimulating hormone

A couple, who is unable to achieve pregnancy over an average period of one year (in women under 35 years of age) or six months (in women above 35 years of age) of unprotected sexual intercourse, is termed as infertile. Infertility can be due to female or male or both reasons. Infertility can be primary or secondary. Primary infertility is when a pregnancy has never been achieved by a couple, and secondary infertility is when atleast one prior pregnancy has been achieved (1).

Thyroid dysfunctions are among the most common diseases in women of reproductive age group (2),(3),(4). Thyroid hormone receptors are present on oocytes that indicate thyroid hormones may influence ovarian functions. It is well-established fact that the menstrual cycle is prolonged in females of hypothyroidism and may lead to infertility because of altered peripheral oestrogen metabolism, hyperprolactinaemia and abnormal release of gonadotropin-releasing hormone (5).

Anti-Müllerian Hormone (AMH) is a dimeric glycoprotein which belongs to the Transforming Growth Factor-beta (TGF-β) super family. AMH acts on tissue growth and differentiation. AMH is produced by the granulosa cells from pre-antral and small antral follicles (6). Serum AMH concentrations are used to evaluate ovarian reserve in females and can be used as a good marker for ovarian reserve (7),(8),(9). Concentration of AMH tends to decrease with age (10). A number of studies support the association between high serum TSH level and decreased ovarian reserve (11),(12).

Thus, the aim of the present study was to find the association between ovarian reserve, measured by AMH concentration and thyroid functions in women with infertility.

Material and Methods

This cross-sectional study was conducted in Department of Biochemistry at Government Medical College, Badaun, Uttar Pradesh, India, from July 2021 to December 2021. The involved women with infertility in the age group of 20-40 years attending the infertility clinic. The ethical clearance was obtained from the concerned Institutional authority (Dated:16/9/2022) and written informed consent was taken from the patients who were enrolled in study.

Sample size calculation: The prevalence of hypothyroidism among women with infertility was found to be 53.7% (13). Considering the absolute margin of error to be 12.5%, the minimum required sample size for undertaking a cross-sectional study (openepi.com) came out to be 62. A total of 118 females were recruited for the study. After exclusion, 78 participants were enrolled in the study.

Inclusion and Exclusion criteria: Women with infertility in age group of 20-40 years, who gave consent to participate were included in the study. Women with other causes of infertility i.e, partner infertility, Polycystic Ovary Syndrome (PCOS), hyperprolactinemia, tubal blockage, ovarian surgery and on treatment for hypothyroidism were excluded from the study.

Systematic random sampling was used to recruit the participants attending the infertility clinic at a tertiary care facility in Badaun. Data was collected two days a week for six months. Every third patient attending the clinic was enrolled in the study starting from any random patient. If the patient was not willing to participate, the third patient starting from her was enrolled, if willing. A maximum of three such patients were enrolled on each day when data was collected.

Study Procedure

Total 118 patients were then subjected to a proforma regarding the demographic details (like age, the period since marriage, the period since the couple has been trying to conceive) and clinical features. Nine patients were excluded based on evidence of their partner’s infertility. Thirteen patients were later diagnosed with having PCOD and hence, excluded from the study.

The blood sample was drawn from the remaining 96 participants. The sample was processed for Serum Thyroid Stimulating Hormone (TSH), free Triiodothyronine (fT3), free Thyroxine (fT4), Prolactin and Anti-Müllerian Hormone (AMH). Elecsys® technology and Cobas e411 analyser (Electrochemiluminescence immunoassay) was used for the quantitative determination of the hormones in human serum (14). Hyperprolactinaemia was observed in 16 samples and hence, they were excluded from the study. On data entry, two values of AMH were identified as outliers and excluded. Test result values of 78 patients were thus, included in the data analysis.

In subclinical hypothyroidism, the TSH is minimally increased while the free T4 stays within the normal range. In subclinical hypothyroidism the serum TSH value of more than 4.2 mIU/L with normal free T4 value between 12-22 pmol/L and in clinical hypothyroidism serum TSH value of more than 4.2 mIU/L with decreased free T4 value less than 12 pmol/L were considered (15),(16),(17). (Table/Fig 1) shows the reference ranges for various parameters used in the study (16),(17),(18),(19),(20),(21),(22).

Statistical Analysis

Data was entered and analysed using the software Statistical Package for Social Sciences (SPSS) version 23.0. The normality of data distribution was evaluated using the Shapiro-Wilk’s Test of Normality. As the values of TSH and fT4 were not distributed normally, the Independent sample Kruskal-Wallis test was used to compare the median values of TSH and fT4 levels in the mentioned subgroups of patients. The Chi-square test was used to establish the association between the categorical variables. Where more than one cell showed a value <5 (in 2×2 tables), Fisher’s-Exact test was used. A p-value of <0.05 was considered significant. The Pearson’s correlation test was used to establish the linear relationship between the variables (TSH and AMH levels). Bivariate regression analysis was used to identify the strength of association between continuous independent variables (age and TSH levels) and the dichotomous dependent variable of whether the female had lower than low normal serum AMH levels. The same test was used to identify the strength of association between the dichotomous independent variable of whether hypothyroidism was present, with the outcome. Multiple regression analysis was used to identify the independent predictors for having lower than low-normal ovarian reserve in women with infertility.

Results

A total of 78 infertile females were included in the study. The mean age of the participants was 30.59±4.67 years. Based on serum AMH values, 22 (28%) females had below normal ovarian reserve i.e., serum AMH value <1 ng/mL, and 56 (72%) females had low normal to normal ovarian reserve i.e., serum AMH value ≥1 ng/mL.

(Table/Fig 2) shows that most of the participants were in the age group of 26 to 30 years. The proportion of females with AMH <1 ng/mL was maximum (36.4%) in the age group of 36 to 40 years and was minimum in the age group 20-25 years. An ascending trend was observed, with a higher proportion of infertile females with lower than low normal ovarian reserve falling in older age groups. The association was found to be statistically significant. The mean age of participants with AMH <1 ng/mL was 33.23±4.28, which was significantly higher than those with AMH value ≥1 ng/mL.

While a quarter of the total sample was found to have hypothyroidism, about half of those with AMH <1 ng/mL had hypothyroidism as compared to only about 16.0% of those with AMH ≥1 ng/mL. This association was found to be highly significant statistically (p-value=0.002). The median TSH value for the study population was 3.2 mIU/L lying within the interquartile range of 2.1 to 4.83. This value was significantly higher in the subgroup of participants with AMH <1 ng/mL, the value being 4.75 mIU/L and was lower (2.8 mIU/L) in the subgroup of participants with AMH ≥1 ng/mL (Table/Fig 2).

It can be seen from (Table/Fig 3) that TSH values and AMH values were related negatively with each other. With a unit rise in TSH values, the AMH value tends to fall by 0.29 units. A 11.6% variance in the AMH values can be attributed to TSH values. (Table/Fig 4) shows that the serum TSH value of participants was negatively correlated with AMH values. So, with a rise in TSH value, the AMH value is supposed to fall. The two variables are weakly correlated, with the value of Pearson’s correlation coefficient=0.341. The relationship was found to be statistically highly significant. A similar relation was seen between age and AMH values with the coefficient=0.346. No significant correlation was present between the variables of age and TSH levels in infertile women.

On bivariate regression analysis, it was concluded that with a unit rise in serum TSH value, the odds of having AMH value of less than 1 ng/mL increases by 1.57, with a 95% confidence interval of 1.13 to 2.19. Similarly with a unit increase in age, the odds of having AMH value <1 ng/mL increases by 1.2 with 95% confidence interval being 1.06-1.35 (Table/Fig 4). After accounting for confounding factors by multiple regression, both the variables continue to predict the outcome independently, thus, the association between the serum TSH levels and low ovarian reserve is independent of whatever association age and serum TSH levels may have with each other. The adjusted Odds Ratio (aOr), hence obtained can be seen in (Table/Fig 4).

It can also be seen from (Table/Fig 4), that when TSH values are converted to binomial variable of whether hypothyroidism is present or not, the presence of hypothyroidism (adjusted for confounding by age) comes out to be a stronger independent predictor of having AMH value less than 1 ng/mL with adjusted Odds Ratios (aOR) (95% confidence interval) being 5.67 (1.71-18.88).

Discussion

In the present study, serum TSH values and AMH values were negatively related with each other. The infertile females with low AMH values had significantly higher values of serum TSH than the females with normal AMH values, showing that the higher values of serum TSH have directly effect on female fertility.

In the present study, the association between serum TSH and fT4 levels and serum AMH as a marker of ovarian reserve in infertile females was examined. Ascending trend was observed, with a higher proportion of infertile females with lower than the low normal ovarian reserve falling in older age groups that was found to be statistically significant. The mean age of participants with AMH <1 ng/mL was 33.23±4.28, which was significantly higher than those with AMH value ≥1 ng/mL (29.5±4.44). This was similar to the study conducted by van Rooij IA et al., that suggest that the concentration of AMH tends to decrease with age (10). Study conducted by Gougeon A et al., showed that decrease in ovarian reserve and its acceleration at the age of 37.5 years (23). The results of present study are also in concordance with the study performed by Krassas G et al., that showed the statistically significant difference between the infertile women and the normal fertile women with regard to the age (5).

The association between serum TSH and AMH levels was found to be highly significant. In the study, conducted by Kabodmehri R et al., inverse relationship between serum TSH levels and ovarian reserve has been observed. they concluded that an increase in TSH from a cut-off point of 1.465 mIU/L in participants over the age of 35 years, is associated with a decrease in ovarian function (20). The study conducted by Sammour HM et al., also concluded that elevated serum TSH is associated with decreased serum AMH in infertile women of reproductive age (24).

Michalakis KG et al., have also shown an association between serum TSH levels and ovarian reserve, and in 18% of patients with low ovarian reserve, TSH levels were higher than 4 μIU/mL (24).

The association between serum TSH and AMH levels have been suggested even in euthyroid patients as the serum TSH levels <3 mIU/mL are associated with better ovarian function and if TSH is higher than this value, they recommended levothyroxine treatment (11),(25).

Kucukler FK et al., found no significant difference between patients with overt or subclinical hypothyroidism and control group in regard to ovarian reserves measured by serum AMH concentration and total antral follicle count. However, lower serum AMH concentration was present in overt and subclinical hypothyroidism patient in their study and they suggested for close follow-up of these patients (26). The current study findings contradict with a number of other studies. A study conducted by Wu J et al., found no significant correlation between the ovarian reserve and thyroid function-related indicators in women with infertility (27). A cross-sectional analytical study by Polyzos NP et al., was conducted in a cohort, all three groups of patients with normal, low, and high ovarian response were included (28). Polyzos NP et al., found no significant correlation between serum TSH and AMH levels and their results were supported by the findings of several other studies (28),(29),(30).

Since, the higher values of serum TSH have direct negative effect on female fertility, it should be addressed as a cause when considering the treatment for infertility in females.

Limitation(s)

Limitations of the present were the inability to evaluate antithyroid antibodies to see the effect of thyroid auto-immunity on ovarian function. Further studies can be done with the evaluation antithyroid antibodies in future.

Conclusion

Significant difference was observed among serum TSH values in the two groups based on whether the serum AMH value was less than 1 ng/mL and equal to or more than 1 ng/mL. The study suggests that the subclinical hypothyroidism has negative impact on the female fertility and increasing age of the females is negatively correlated with the ovarian reserve.

Authors’ contributions: SC contributed to conception and study design. SSS did data collection, drafted the manuscript and revised it. SS performed statistical analysis. All authors read and approved the final manuscript.

References

1.
Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HG, Behre HM, et al. World Health Organization reference value for human semen characteristics. Hum Reprod Update. 2010;16(3):231-45. [crossref] [PubMed]
2.
Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: A twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995;43(1):55-68. [crossref] [PubMed]
3.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160(4):526-34. [crossref] [PubMed]
4.
Aoki Y, Belin RM, Clickner R, Jeffries R, Phillips L, Mahaffey KR. Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002). Thyroid. 2007;17(12):1211-23. [crossref] [PubMed]
5.
Krassas G, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31(5):702-55. [crossref] [PubMed]
6.
Sammour HM, Abuelghar WM, El-Salam NE, Ahmed HH. TSH and AMH in infertile women. The Egyptian Journal of Hospital Medicine. 2017;69 (2):1814-22. [crossref]
7.
Anderson R, Nelson S, Wallace W. Measuring anti-Müllerian hormone for the assessment of ovarian reserve: When and for whom is it indicated? Maturitas. 2012;71(1):28-33. [crossref] [PubMed]
8.
Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve. A committee opinion. Fertil Steril. 2015;103(3):e9-17. [crossref] [PubMed]
9.
Seifer DB, MacLaughlin DT, Christian BP, Feng B, Shelde RM. Early follicular serum Müllerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertil Steril. 2002;77:468-71. [crossref] [PubMed]
10.
van Rooij IA, Broekmans FJ, Scheffer GJ, Looman CWN, Dik F Habbema J, de Jong FH, et al. Serum antimüllerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: A longitudinal study. Fertil Steril. 2005;83(4):979-87. [crossref] [PubMed]
11.
Weghofer A, Barad DH, Darmon S, Kushnir VA, Gleicher N. What affects functional ovarian reserve, thyroid function or thyroid autoimmunity? Reprod Biol Endocrinol. 2016;14(1):01-06. [crossref] [PubMed]
12.
Ak?n EÖ, Aycan Z. Evaluation of the ovarian reserve in adolescents with Hashimoto’s thyroiditis using serum anti-müllerian hormone levels. J Clin Res Pediatr Endocrinol. 2018;10(4):331.
13.
Priya DM, Akhtar N, Ahmad J. Prevalence of hypothyroidism in infertile women and evaluation of response of treatment for hypothyroidism on infertility. Indian J Endocrinol Metab. 2015;19(4):504-06. [crossref] [PubMed]
14.
cobas e 411 analyzer. Available from: https://diagnostics.roche.com/global/en/products/instruments/cobas-e-411-ins-502.
15.
Bishop ML, Fody EP, Schoeff LE. Clinical chemistry: Principles, Techniques, and Correlations/7th ed, Philadelphia, P, Lippincott Williams & Wilkins, a Wolters Kluwer business; 2013; pg 520.
16.
Elecsys TSH. Available from: http://labogids.sintmaria.be/sites/default/files/files/tsh_2018-05_v24.pdf (last accessed on: 15.10.2022).
17.
FT4 II. Available from: http://labogids.sintmaria.be/sites/default/files/files/ft4_ii_2013-05_v2.pdf (last accessed on: 15.10.2022).
18.
FT3 III. Available from: http://labogids.sintmaria.be/sites/default/files/files/ft3_iii_2017-03_v2.pdf (last accessed on: 15.10.2022).
19.
Elecsys® AMH (Anti-Mullerian Hormone). Available from: https://diagnostics.roche.com/in/en_gb/products/params/elecsys-amh-anti-mullerian hormone.html.
20.
Kabodmehri R, Sharami SH, Sorouri ZZ, Gashti NG, Milani F, Chaypaz Z, et al. The relationship between thyroid function and ovarian reserve: A prospective cross sectional study. Thyroid Res. 2021;14(1):22. [crossref] [PubMed]
21.
Elecsys Prolactin II. Available from: http://labogids.sintmaria.be/sites/default/files/files/prolactin_ii_2019-01_v9.pdf (last accessed on: 15.10.2022).
22.
Ficicioglu C, Cenksoy PO, Yildirim G, Kaspar C. Which cut-off value of serum anti-Müllerian hormone level can predict poor ovarian reserve, poor ovarian response to stimulation and in vitro fertilization success? A prospective data analysis. Gynecol Endocrinol. 2014;30(5):372-76. [crossref] [PubMed]
23.
Gougeon A, Ecochard R, Thalabard JC. Age-related changes of the population of human ovarian follicles: Increase in the disappearance rate of non-growing and early-growing follicles in aging women. Biol Reprod. 1994;50(3):653-63. [crossref] [PubMed]
24.
Michalakis KG, Mesen TB, Brayboy LM, Yu B, Richter KS, Levy M, et al. Subclinical elevations of thyroid-stimulating hormone and assisted reproductive technology outcomes. Fertil Steril. 2011;95(8):2634-37. [crossref] [PubMed]
25.
Rao M, Wang H, Zhao S, Liu J, Wen Y, Wu Z, et al. Subclinical hypothyroidism is associated with lower ovarian reserve in women aged 35 years or older. Thyroid. 2020;30(1):95-05. [crossref] [PubMed]
26.
Kucukler FK, Gorkem U, Simsek Y, Kocabas R, Guler S. Evaluation of ovarian reserve in women with overt or subclinical hypothyroidism. Arch Med Sci. 2018;14(3):521-26. [crossref] [PubMed]
27.
Wu J, Zhao YJ, Wang M, Tang MQ, Liu Yf. Correlation analysis between ovarian reserve and thyroid hormone levels in infertile women of reproductive age. Front Endocrinol. 2021;12:745199. [crossref] [PubMed]
28.
Polyzos NP, Sakkas E, Vaiarelli A, Poppe K, Camus M, Tournaye H. Thyroid autoimmunity, hypothyroidism and ovarian reserve: A cross-sectional study of 5000 women based on age-specific AMH values. Hum Reprod. 2015;30(7):1690-96. [crossref] [PubMed]
29.
Chen CW, Huang YL, Tzeng CR, Huang RL, Chen CH. Idiopathic low ovarian reserve is associated with more frequent positive thyroid peroxidase antibodies. Thyroid. 2017;27(9):1194-200. [crossref] [PubMed]
30.
Korevaar TIM, Mínguez-Alarcón L, Messerlian C, de Poortere RA, Williams PL, Broeren MA, et al. Association of thyroid function and autoimmunity with ovarian reserve in women seeking infertility care. Thyroid. 2018;28(10):1349-58. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/58517.17085

Date of Submission: Jun 18, 2022
Date of Peer Review: Jul 16, 2022
Date of Acceptance: Oct 27, 2022
Date of Publishing: Nov 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jun 22, 2022
• Manual Googling: Oct 17, 2022
• iThenticate Software: Oct 25, 2022 (18%)

ETYMOLOGY: Author Origin

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com