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

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On Jan 2020

Important Notice

Original article / research
Year : 2012 | Month : April | Volume : 6 | Issue : 2 | Page : 166 - 168 Full Version

Ovarian Reserve Tests for Sub-fertility: When to Intervene


Published: April 1, 2012 | DOI: https://doi.org/10.7860/JCDR/2012/.1940
Kalaiselvi V.S., Saikumar P., Prabhu K.

1. Associate Professor, Department of Bio Chemistry 2. Professor, Department of Physiology 3. Associate Professor, Department of Anatomy Sree Balaji Medical College and hospital, Chennai, India.

Correspondence Address :
Dr. Kalaiselvi V.S., M.D.
Assoicate Professor
Department of Biochemistry
Sree Balaji Medical College and hospital,
No. 7, CLC Works Road, Chrompet,
Chennai- 600 044, India.
Phone: 9884218580
E-mail: kalai.selvi51@yahoo.com

Abstract

Back ground:
During the past two decades , a greater majority of women have been known to plan their pregnancies in the thirties, often because of carrier priorities and as a result, they have to face the consequences of their declining fecundity (reproductive potential). Hence, it was decided to assess the ovarian reserve, which is an estimate of the follicular pool, the production of follicles being the primary function of the ovary. Our work highlights the assessment of the ovarian reserve in sub-fertile women.
Aim:
To assess the ovarian reserve in subfertile women by doing hormonal assays and by using ultrasonographic methods.
Materials and Methods:
50 subfertile women of the childbearing age, without an issue even after 3 years of unprotected sexual acts, were included in this study. The subjects who were under study were divided into two groups. Group 1- sub-fertile women with their ages ranging from 20-25 years and Group 2- sub-fertile women of comparatively older ages, whose ages ranged from 26-33 years. For both the groups, hormones like the Follicular Stimulating Hormone (FSH) and oestradiol (E2) were measured by ELISA. The Antral Follicular Count (AFC) and the ovarian volume (OV) were measured by transvaginal ultrasound. The correlations between the various parameters were analyzed and the StudentÂ’s t-test was performed between the two groups by using SPSS.
Results:
Statistically significant correlations between age and antral follicular count (AFC), ovarian volume (OV) and FSH were observed. Elevated FSH, and decreased AFC and OV were observed in sub-fertile women of comparatively older ages and their mean values were also statistically different between the two groups.
Conclusion:
Women with elevated FSH and E2 and decreased AFC and OV should be insisted to proceed for Assited Reproductive Technique (ART) as early as possible, irrespective of their ages, as parenthood is undeniably one of the most universally desired goals in adulthood.

Keywords

FSH, Oestradiol ovarian reserve

INTRODUCTION
The production of mature and viable oocytes is the primary function of the female ovary, which should be capable of fertilization, subsequent embryo development and implantation. Women are born with a pre-determined number of ovarian follicles, approximately two million, and these are subsequently reduced by apoptosis and ovulation. So, at birth, the ovary contains a finite number of oocytes which are available for folliculogenesis. This finite number of available oocytes is termed as the ovarian reserve. None of the ovarian reserve tests directly measures the total number of actual oocytes. Rather, it is assumed that the antral follicular count is directly related to the total oocyte pool. The ovarian volume and AFC which can be measured by Trans Vaginal Ultrasonography (TVS), can be useful indicators of the menopausal status and the ovarian function (1). Day 3 FSH has also been considered as a bio marker of the ovarian reserve, as it provides a glimpse of how well the hypothalamic pituitary gonadal axis is functioning through ovarian feedback to the pituitary (2). Day 3 oestradiol has also been estimated to assess the ovarian reserve (OR), as oestradiol is a product of the granulosa cells and as it can be considered as a reflection of the follicular activity. The remaining reproductive life time can be assessed by the ovarian reserve test. So, the success of IVF (in vitro fertilization) and ART (Assisted Reproductive Technique) can be predicted by estimating the ovarian reserve. This work highlights the assay of hormones Original Article Biochemistry Section and the ultrasonographic measurement of the ovarian volume and the antral follicular count in sub fertile women of younger ages and comparatively little older ages.

Material and Methods

This study was approved by the institutional ethical committee. Fifty women of the child bearing ages, but with out an issue even after 3 years of unprotected sexual acts, were included in this study. An informed consent was obtained from all the participants. The subjects who were under study were divided into two groups. Group 1 (n = 25); sub-fertile women with their ages ranging from 20-25 years. Group 2 (n = 25); sub-fertile women with comparatively older ages which ranged from 26-33 years. The general profile like age, height, weight and body mass index (BMI) were also recorded.
Exclusion Criteria
Thyroid disorders, a history of ovarian surgery, an irregular menstrual cycle and ovarian abnormalities which was assessed by the trans vaginal ultrasonogram method, hormonal conception and male infertility were excluded from this study. The ovarian volume and the antral follicular count were measured by Transvaginal Ultrasonograph Measurements (TVS). Trans vaginal ultrasound was performed to measure the number of antral follicles as well as the volume of both the ovaries. It was carried out on the cycle days 3-10. The volume of each ovary was determined by measuring the three perpendicular diameters and by applying the formula for the volume of an ellipsoid. Each ovary was scanned in three dimensions – D1 (longitudinal), D2 (anteroposterior) and D3 (transverse).The volume of each ovary was calculated from the three dimensions by applying the equation for the volume of an ellipsoid (D1*D2*D3*0.523cm3) (3). The volumes of both the ovaries were added to calculate the total ovarian volume (4), (5). All the sonography measurements were done by the same observer by using a 7.5 MHz trans vaginal probe. The examination of the ovary was established by scanning it from the outer to the inner margin. All the follicles which were 2-10 mm in size were measured and counted in each ovary. The sum of both the counts was the antral follicle count.
Hormonal Assay
Both the blood sampling and the ultrasonographic measurements were performed on the same day. Hormones like FSH, LH and E2 were measured in plasma by ELISA. The specimens were stored at -200C until they were processed.

Results

A correlation test was done to find the correlation between the variables like, BMI, FSH, E2, AFC, OV and age for both the groups, and the test of significance of the above variables was assessed between the two groups. From the correlation table, the following results were inferred. Age was inversely related to the antral follicular count (r= -0.557, p = 0.001), which was statistically significant and it was also related to the ovarian volume (r=-0.278, p=0.075), as shown in (Table/Fig 1). The mean BMI was higher in Group 2 than Group 1. The mean ovarian volume in Group1 was 16.3cm3 and in Group 2, it was 7.65 cm3. The mean value of the OV was also statistically significant. Five women in Group 2 had the OV below 3cm3. The mean follicular number in both the ovaries was 16 in Group 1 and 5.1 in Group2 (Table/Fig 2). This was also statistically significant. The elevated levels of FSH was more in Group 2 and of these, five women showed an elevation of above 15 IU/l in that group.

Discussion

During the past two decades, a greater majority of women have been known to plan their pregnancy in their thirties, often because of career priorities and as a result, they have to face the consequences of their declining fecundity (reproductive potential). The importance of age in fecundity has been shown by many observations. Although age is an important factor in sub-fertility , it does not exactly predict the reproductive potential. The estimation of serum FSH on day 3 is an indirect method of assessing the ovarian reserve. In one study by Martin et al (1996), no pregnancies were found in the cycles with a day 3 FSH concentration of above 20 IU/ml, while in other studies, age was seen to be a better predictor for the IVF outcome than the basal FSH concentration (6). Another study by Ahmed Ebbiary et al (1994) showed that subfertile women with a high FSH concentration had poorer follicular growth in a natural cycle as compared to subfertile women with a normal FSH concentration (7). Previous studies have revealed that women with normal ovulatory cycles had subtle elevations in the FSH in their early 30s and that these levels tended to increase with age.The day 3 FSH has been believed to represent the basal level or the non-suppressed level of the FSH reserve. This reflects the number and the quality of the oocytes, which at any given age, are available to produce a dominant follicle late in the follicular phase of the menstrual cycle and its value can be elevated due to the occurrence of rapid folliculogenesis (8). In our study, we noticed an elevated FSH level of above 15 IU/L in sub fertile women of comparatively older age. The authors of this article attributed this decline to a diminished ovarian reserve (9). Similarly, oestradiol was elevated significantly in the sub-fertile subjects of older ages, which was also an indication of diminished ovarian reserve. The oestradiol concentration, in combination with the basal FSH value and age was found to be a useful predictor of the fertility potential (10). But some authors found no relationship between the day 3 oestradiol concentration and the pregnancy rates (11). The number of antral follicles is related to the reproductive age in women with proven fertility and this might also reflect the ovarian reserve (4). It was found to be less in the sub-fertile population of older ages. The studies by Haadsma et al (2007) showed that the small antral follicles correlated not only with age, but also independently with the results of the various other endocrine ovarian reserve tests like Anti Mullerian Hormone (AMH) (12). During a womanÂ’s life, the ovarian volume changes from 0.7 cm3 at the age of 10 years to 5.8 cm3 at the age of 18 years (13). However, at the age of 40 years, the ovaries tend to decrease in size and they decrease even further after menopause. Syrop et alÂ’s (1995) study concluded that the OV might be an important predictor of the OR (5). But, Tomas et al (1999) showed that the ovarian volume was found to be a predictor of the number of growing follicles, but not of the number of recovered oocytes (14). In our study, the ovarian volume in the sub fertile population of older ages was lesser than that in the subfertile population of younger ages. Although age is an important factor in sub fertility, it is not very exact in predicting the reproductive potential. Some women will be unable to conceive either early or in their thirties, while others become pregnant in their forties. The ovarian reserve appears to be responsible for these differences (15). Many tests have been developed to screen the diminished ovarian Reserve.

Conclusion

This study strongly emphasize that women with elevated Oestradiol, FSH and low AFC,OV should be insisted to proceed for ART as early as possible, irrespective of their ages. The above mentioned values in women of younger ages also are to be intervened for early counseling to go ahead for ART, as parenthood is undeniably one of the most universally desired goals in adult hood. So, an early intervention and educative counseling will help in reducing the rate of subfertility in our population.

References

1.
Flaws JA, Langenberg P, Babus JK, Hirshfield AN, Sharara FI. Ovarian volume and antral follicle counts as indicators of the menopausal status. Menopuase 2001; 8:175-80.
2.
Barnhart K, Osheroff J. Follicle stimulating hormone as a predictor of fertility. Curr. Opin. Obstet. Gynecol 1998;10:227-32.
3.
Wallace HW, Kelsey TW. Ovarian reserve and reproductive age may be determined from the measurement of the ovarian volume by transvaginal sonography. Human Reproduction 2004;19: 1612-17.
4.
Scheffer GJ, Broekmans FJM, Dorland M, et al. Antral follicle counts which are obtained by transvaginal ultrasonography are related to age in women with proven natural fertility. Fertil Steril 1999; 72:845-51.
5.
Syrop CH, Willhotie A, Van Voorhis BJ. Ovarian volume: a novel outcome predictor for assisted reproduction. Fertil. Steril 1995; 64: 1167-71.
6.
Martin JSB, Nisker JA, Tummon IS, et al. The future in vitro fertilization pregnancy potential of women with variable elevated day 3 folliclestimulating hormone levels. Fertil . Steril 1996; 65 :1238-40.
7.
Ahmed Ebbiary NA, Lenton EA, Salt C, et al. The significance of the elevated basal follicle stimulating hormone in regularly menstruating infertile women. Hum. Reprod 1994; 9: 245-52.
8.
Bancsi LF, Broekmans FJ, Eijkemans MJ, De Jong FH, Habbema JD, te Velde ER. Performance of the basal follicle-stimulating hormone in the prediction of poor ovarian response and failure to become pregnant after in vitro fertilization: A meta-analysis. Fertil Steril 2003; 79: 1091-100.
9.
Perloe M, Levy DP, Sills ES. Strategies for ascertaining the ovarian reserve among women who were suspected to be having subfertility. Int J Fertil Womens Med 2000: 215-24.
10.
Buyalos RP, Daneshmand S, Brzechffa PR. Basal estradiol and folliclestimulating hormone levels predict the fecundity in women of advanced reproductive ages, who undergo ovulation induction therapy. Fertil. Steril 1997; 68: 272-77.
11.
Scott RT, Toner JP, Muasher SL, et al. The follicle-stimuating hormone levels on the cycle day 3 are predictive of the in-vitro fertilization outcome. Fertil. Steril 1989; 51: 651-54.
12.
Haadsma ML, Bukman A, Groen H, Roeloffzen EMA, Groenewoud ER, Heineman MJ, et al. The number of small antral follicles (2-6 mm) determines the outcome of the endocrine ovarian reserve tests in a subfertile population. Human Reproduction 2007 ;22: 1925-31.
13.
Ivarsson SA, Nilsson KO, Persson PH. Ultrasonography of the pelvic organs in prepubertal and postpubertal girls. Arch Dis Child 1983;58:352-54.
14.
Tomas C, Nuojua-Huttunen S, Martikainen H. Pre-treatment transvaginal ultrasound examination predicts the ovarian responsiveness to gonadotrophins in in-vitro fertilization. Hum. Reprod 1997 ;12: 220-23.
15.
Bukman A, Heineman MJ. Ovarian reserve testing and the use of prognostic models in patients with sub fertility. Hum. Reprod 2001;7 (6): 581-90.

DOI and Others

DOI: JCDR/3909:1940

Financial OR OTHER COMPETING INTERESTS:
None.


Date Of Submission: Oct 24, 2011
Date Of Peer Review: Dec 25, 2011
Date Of Acceptance: Jan 10, 2012
Date Of Publishing: Apr 15, 2012

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