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 Table of Contents  
Year : 2017  |  Volume : 4  |  Issue : 2  |  Page : 74-80

Ovarian reserve

1 Department of Obstetrics and Gynaecology, Deen Dayal Upadhyay Hospital, Hari Nagar, New Delhi, India
2 IVF & Reproductive Medicine, Max Multispeciality Hospitals, Panchsheel Saket, Patparganj, New Delhi, India
3 Department of Obstetrics & Gyanaecology, Subharati Medical College, Meerut, Uttar Pradesh, India

Date of Web Publication3-Aug-2018

Correspondence Address:
Dr. Pinkee Saxena
Deen Dayal Upadhyay Hospital, Hari Nagar, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/fsr.fsr_6_18

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Nowadays more and more couples are delaying childbirth. As the age of the couples advances, their chances of achieving pregnancy decrease. This is due to the natural process of ageing of gonads. During counselling and treatment of infertile couples, clinicians are often faced with questions like what is the chance of conception. Hence there is need to test for functional ovarian reserve. An ideal ovarian reserve test is affordable, convenient, reproducible and sensitive. Various clinical and biochemical markers have been used to predict the same. These tests help to predict the poor response or hyper response to ovarian stimulation and help to formulate the treatment plans in infertile couple. They however cannot predict future fertility or occurrence of pregnancy.

Keywords: AFC, AMH, ovarian reserve

How to cite this article:
Saxena P, Ghumman S, Prateek S. Ovarian reserve. Fertil Sci Res 2017;4:74-80

How to cite this URL:
Saxena P, Ghumman S, Prateek S. Ovarian reserve. Fertil Sci Res [serial online] 2017 [cited 2022 Oct 1];4:74-80. Available from: https://www.fertilityscienceresearch.org/text.asp?2017/4/2/74/238552

  Introduction Top

Changing lifestyle has led to delay in childbearing in most of the couples. The postponement of maternity has led to an increased demand of assisted reproduction technology. Hence, there is need for the functional evaluation of the ovarian reserve to counsel infertile couple regarding their reproductive chance.[1] It also guides the clinician to decide about the treatment protocols and individualize the treatment.

The ovary of a female fetus has 6 to 7 million oocytes at 20 weeks. Atresia of these oocytes starts in utero. At the time of birth, 1 to 2 million oocytes are available. The rate of follicular atresia then slows down, and at puberty, 300,000 to 400,000 oocytes remain. During each ovulatory cycle, a cohort of follicles gets recruited, of which, one grows to become the dominant follicle, and the rest undergo atresia. At the time of menopause, the number falls to below 1000.

Ovarian reserve is a complex clinical phenomenon that is greatly influenced by age, genetics and the environment variable. The decline in woman’s ovarian reserve is an irreversible phenomenon. The rate at which a woman loses her primordial follicle varies from person to person. Ovarian reserve refers to the residual oocyte granulosa cell that is available for fertilization at any given age. The quantitative and qualitative decline of these cells is seen with advancing age. Ovarian reserve provides information regarding the follicles that can be stimulated and the oocyte that can be retrieved from the ovary.

Treating clinicians are often faced with the challenge to predict the fertility potential of women. The ovarian reserve tests add more prognostic information to the counseling of infertile couple. It helps to identify patients who are likely to have poor response or hyperresponse to gonadotrophin stimulation, but it cannot predict clinically important outcome such as pregnancy. It helps to differentiate patients with normal ovarian reserve from those with diminished ovarian reserve and helps in deciding treatment protocols in women with diminished reserve. It also helps in avoiding aggressive treatment in women with normal reserve. It, however, should not be used to exclude an infertile couple from seeking assisted reproductive technology (ART).

Various clinical and biochemical markers have been studied to test for the ovarian reserve. Sharara and Scott emphasized that an ideal ovarian reserve test should be easy to measure, minimally invasive, inexpensive and should have good predictive value.[2]

  Clinical markers Top

Common clinical markers used to determine the ovarian reserve are age and menstrual cycle length (MCL).


Age is a factor that has been used since long to predict the quality and quantity of the ovarian reserve. Studies have shown that the fecundability declines after the early 30s.[3] The prevalence of infertility increases significantly after the age of 35 years, and by the age of 45, around 99% of the patients are expected to be infertile.[4] Genetic factors, smoking, infections and adnexal surgeries are the other determinants of diminished ovarian reserve in older women.[5] Age alone has a limited value in predicting individual ovarian responses.[6] In a recent study, however, Scheffer et al. have stated that age is the best predictor of embryo quality.[7] Tehraninezhad et al. in their study[8] have also found age to be a superior variable to predict clinical pregnancy.

Menstrual cycle

MCL is usually determined by the rate and quality of growth of the follicle and the duration of the follicular phase. The pattern of menstrual cycle in a woman remains consistent until the late 40s, after which a gradual shortening in cycle length is seen. In addition, in the late 30s, a higher serum level of follicular stimulating hormone (FSH) and lower serum levels of inhibin are seen in women.[9]

Brodin et al.[10] in their study found a correlation among MCL and pregnancy and delivery rate, independent of age. They observed that in women with cycles >34 days, delivery rate was twice as compared with those having cycles <26 days. A significant association of MCL was also noted with the response of the ovary to gonadotropin drugs and the quality of the embryos obtained in IVF/ICSI cycles.

  Biochemical markers Top

They can be either basal measurement or dynamic tests. Basal tests include FSH, estradiol (E2), inhibin B, anti-Müllerian hormone (AMH) and ultrasonography and dynamic tests include clomiphene citrate challenge test (CCCT) and other tests. Basal test measures are dependent on changes that occur in the ovarian milieu during the follicular growth, and it reflects the reserve of the ageing ovary. The dynamic test evaluates the response of the hypothalamic–pituitary–ovarian axis to stimulation.

Follicle stimulating hormone

Early follicular phase serum FSH is the commonly used endocrine test for determining the ovarian reserve. It is based on the feedback inhibition of FSH secretion by ovarian hormones and, hence, is an indirect marker of the ovarian reserve. At the beginning of the menstrual cycle, the E2 and inhibin B levels inhibit FSH secretion from the pituitary. In women with diminished ovarian reserve, the production of ovarian hormones is insufficient, and this leads to elevated pituitary FSH secretion.

Van der Steeg et al. studied the predictive value of basal FSH for achieving spontaneous pregnancy in ovulatory subfertile women younger than 40 years. He said that when FSH levels exceeded 8 IU/L, there was a reduced chance of achieving pregnancy.[11] Ashrafi et al. in their study observed that in women with serum FSH levels ≥15 IU/mL, fewer oocytes were aspirated, and they had a higher cycles cancellation rate than women with lower FSH levels, with no significant difference in gonadotropin doses administered.[12] Klinkert et al. observed that the pregnancy rate was less in women with FSH levels ≥15 IU/L as compared to those with lower levels; however, this was not statistically significant.[13] Luna et al. in their study observed that pregnancy rates in women aged <35 years with elevated basal FSH were higher than those of older women with normal levels of the hormone.[14] They recommended that young women with elevated basal FSH should be counseled differently from older women. Van Montfrans et al. in his study also said that basal FSH should not be the decisive factor to the initial management of infertile women with regular menstrual cycles.[15] A recent study has also stated that FSH is less reliable than other markers such as AMH and antral follicle count (AFC) for assessing the ovarian reserve.[16] Hence, high FSH levels should not be used as the criterion alone to exclude women from ART.


E2 levels are a reflection of the ovarian response. Early elevations in basal serum E2 are due to the advanced follicular development and the early selection of a dominant follicle, as seen in older women, due to rising FSH levels.[9] It has been observed that women with E2 levels <20 pg/mL or ≥80 pg/mL have a higher artificial reproductive techniques (ART) cycle cancellation rate.[17] Combining E2 with FSH on cycle day 3 is shown to have reduced the incidence of false-negative tests obtained when FSH alone was used. The elevation of both indicates poor ovarian response.

E2, however, has low predictive accuracy and lacks high sensitivity and specificity cutoff levels.[18] It may be used as a guide for starting stimulation with gonadotropins; however, it should not be used to exclude couples from ART programs.

Inhibin B

Inhibins are glycoproteins secreted by the granulosa and theca cells. It plays a major role in the selection of the dominant follicle and has a regulatory effect on the secretion of FSH.[19] Women with inhibin B concentration levels ≥45 pg/mL have increased oocyte retrieval rate and lesser cycle cancellation rate, as observed by Seifer et al.[20] However, few studies have shown that inhibin B alone is not a very useful marker of the ovarian reserve.[21] The routine use of inhibin B is, hence, not recommended in infertile couples.

Anti-Müllerian hormone

AMH is a glycoprotein hormone that is expressed by the granulosa cells of the secondary, preantral and small antral follicles <4 mm in size. As the follicles grow, AMH expression decreases. Further follicular growth is then determined by FSH action.[22] AMH, thus, acts as a modulator of follicle recruitment and plays an important role in folliculogenesis. Compared to other markers, AMH levels do not vary much during the menstrual cycle and, hence, is reproducible.[22] Serum AMH has also been shown to be a reliable marker for ovarian ageing and in predicting reproductive status.[23]

Women with polycystic ovary syndrome have an increased number of antral follicles compared with normal women.[24]. Serum AMH levels are, hence, found to be two to three times higher in women with PCOS.[25] Women with low AMH levels prior to IVF may have either an increased risk of cycle cancellation or poor response to stimulation. Van Rooij et al. observed that serum AMH levels correlated well with preinduction AFC and the number of oocytes retrieved in ART cycles.[26] In a meta-analysis, it was seen that AMH levels have similar predictive value as AFC in identifying poor responder.[27]

Some have proposed a cutoff value range of 0.7-0.75 ng/mL for AMH for the identification of poor responders.[28],[29] Although there seems to be a good sensitivity and specificity, it is seen that the prevalence of young women with AMH levels <0.7 ng/mL is low. Others have considered serum AMH levels lower than 0.1-0.35 ng/mL as cutoff to minimize false positives. It identifies patients who are at very high risk for cycle cancellation.[30],[31]

High AMH levels before IVF are also useful in identifying women at risk for hyperresponse and ovarian hyperstimulation syndrome (OHSS). Vembu in his study has suggested a cutoff value of serum AMH to predict the hyperresponse in PCOS group as 6.85 ng/mL and in non-PCOS group as 4.85 ng/mL.[32] In these patients, starting a low dose of FSH followed by the use of GnRH antagonists or using GnRH antagonist for the triggering of ovulation instead of hCG[33] can be done to prevent the development of OHSS.

The measurement of AMH levels may be useful in the prediction of poor response and cycle cancellation as well as hyperresponse and ovarian hyperstimulation in ART. It also plays a role in the individualization of treatment strategies in patients undergoing in vitro fertilization (IVF) treatment. However, the AMH cannot predict the qualitative ovarian response in ART or pregnancy.

  Ovarian ultrasonography Top

Antral follicle count

AFC is the total number of follicles observed in both the ovaries in the early follicular phase using transvaginal ultrasonography. It is a very reliable marker of the ovarian reserve.[30],[34] A count of 8-10 is considered as a predictor of a normal response. The diameters of the follicle used to define antral follicles ranges from 2 to 10 mm. Haadsma et al. in their study observed that the number of small antral follicles, 2-6 mm in size, declines with age, but that of 7-10 mm in size remains constant. They said that the small antral follicle correlates well with the ovarian reserve tests and appears to represent functional ovarian reserve better.[35]

Compared to other tests, AFC has the best discriminating potential for a poor ovarian response. It, however, lacks the sensitivity and specificity to predict the nonoccurrence of pregnancy.[36] The presence of more than 14 antral follicles is considered to be a predictor of hyperresponse.[37]

Maseelall et al. in their study observed that women with AFC ≥11 (follicles measuring between 2 and 10 mm present on both the ovaries) were more likely to have a live birth.[38] In a meta-analysis, it was seen that women with AFC ≤4 were 8.7 times [95% confidence interval (95% CI 2.4 to 31.7) more likely not to be pregnant and 37 times (95% CI 13.68–100.45) more likely to have their cycle cancelled than women with a AFC of four or more.[39] The sensitivity and specificity of AFC to predict cycle cancellation was 67 and 95%, respectively. However, due to 12% sensitivity to predict no pregnancy and 67% sensitivity to predict cycle cancellation,[39] AFC must not be used as a criterion for ART exclusion. It is a useful tool for counseling on the low probability of achieving pregnancy and determining individualized treatment protocols in IVF cycles.

Ovarian volume

The routine use of ovarian volume as a predictor of ovarian reserve is controversial. The study conducted by Gibreel et al. observed 93% (95% CI 87 to 97) and 92% (95% CI 89 to 94) specificities for the prediction of nonpregnancy and cycle cancellation, respectively, with a 3.0 mL cutoff.[39] In a meta-analysis performed by Hendriks et al., the predictive value of ovarian volume for poor response to stimulation was inferior,[36] as noted by Broekmans et al. in a previous study.[18]

Ovarian blood flow

Ovarian blood flow has been studied in natural and stimulated reproductive cycles.[40] Shrestha et al. in their study showed that high-grade ovarian perifollicular blood flow in the early follicular phase during ovarian stimulation was associated with a higher clinical pregnancy rate.[41] However, the value of ovarian blood flow is still indeterminate.[39]

  Others Top

Clomiphene citrate challenge test

CCCT was first described by Navot et al. In this test, 100 mg clomiphene citrate was given from day 5 for 5 days. Serum FSH, LH and E2 levels were determined on day 3 and day 10. Diminished ovarian reserve was determined by day 3 FSH levels >14.9 mIU/mL or day 10 FSH levels > day 3 FSH level.[42] However, a meta-analysis has shown that CCCT is no better than basal FSH in predicting a clinical pregnancy.[43]

Exogenous FSH ovarian reserve test

The exogenous FSH ovarian reserve test (EFORT) measures the increase in E2 and inhibin B 24 h after the administration of 300 IU of recombinant FSH on cycle day 3.[44] It tests the functional response of the ovary. Increased levels of E2 and inhibin B after EFORT has a good predictive value for the number of ovarian dominant follicles that can be obtained after stimulation. However, this test lacks uniformity.

Gonadotrophin releasing hormone agonist stimulation test

In this test, serum estradiol is measured on day 2 of the cycle followed by the subcutaneous administration of gonadotropin analogue (triptorelin 100 μg). E2 levels are measured 24 h later and on day 3, and values are compared. A rise in E2 level is considered indicative of good ovarian reserve. It is found to have a good ability for the prediction of poor ovarian reserve, but is not superior to inhibin B or AFC in this regard.[45]


Ovarian reserve testing should be performed for women older than 35 years who have not conceived after 6 months of attempting pregnancy and women at a high risk of diminished ovarian reserve.[46]

According to the NICE guidelines,[47] a women is said to have sufficient ovarian reserve if she either has an AFC of >4 or serum AMH level >5.4 pmol/L or serum FSH level <8.9 IU/I.

As already stated, an ideal ovarian reserve test should be convenient, reproducible with little intracycle or intercycle variability and demonstrate high specificity to minimize the risk of wrong diagnosis of diminished ovarian reserve. It should also have the ability to identify those at risk of developing ovarian hyperstimulation. Tests such as FSH are an indirect measure of the ovarian reserve and have substantial intracycle or intercycle variability. The provocative tests such as CCCT have not been commonly performed due to the expense and inconvenience, because they require more than one visit.

A large body of evidence has demonstrated a greater clinical value of AMH and AFC compared to FSH.[16],[48] AMH has been shown to have better reliability than other markers to predict ovarian reserve and response to stimulation.[49],[50] It is a highly sensitive and superior real-time biomarker, which tells us about the pool of primordial follicle.[51] Other tests are based on the ovarian response to the hormones produced by the follicle during folliculogenesis. AFC measures only antral follicles, and results are operator dependent.

At times, discordance is seen in these ovarian reserve tests. In a large study of 5354 women[52] tested, one in five had discordant AMH and FSH values defined as AMH <0.8 (concerning) with FSH <10 (reassuring) or AMH ≥0.8 (reassuring) with FSH ≥10 (concerning). Of the women with reassuring FSH values (n = 4469), the concerning AMH values were found in one in five women in a highly age-dependent fashion, ranging from one in 11 women under 35 years of age to one in three women above 40 years of age. This can be explained by the fact that AMH is more sensitive, and its levels decline much earlier than the rise in FSH levels. This is due to normal ovarian ageing. On the other hand, of the women with reassuring AMH values (n = 3742), one in 18 had concerning FSH values, a frequency that did not vary in a statistically significant fashion by age.A total of 366 infertile patients undergoing IVF were studied by Gleicher et al.[53] They observed that the oocyte yields significantly decreased from patients having normal AMH and FSH to normal AMH/abnormal FSH or normal FSH/abnormal AMH and both abnormal. Except at very young and very old ages, normal AMH level is a better predictor of higher oocyte yields than normal FSH level. Women with normal AMH level but abnormal FSH level do not follow far behind until age 42. Beyond 42 years, normal FSH level predicts good oocyte yield even with abnormally low AMH level.

An evaluation of ovarian response in women undergoing IVF with discordant baseline serum AMH level and AFC was performed on 1046 women.[54] Among them, 32.2% had discordant AMH and AFC results. When AMH and AFC were discordant, it was seen that the ovarian responsiveness was intermediate between that when both were concordant on either end. Women having higher AMH within the same AFC quartile had a higher number of retrieved oocytes and cumulative live-birth rate.

  Conclusion Top

Ovarian reserve test is an indirect marker of woman’s follicular pool, which tells us about her sensitivity to ovarian stimulation and success with these procedures. They, however, cannot predict future fertility or the timing of decline or the cessation of future fertility. Currently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, but they occupy an important place in initial counseling, predicting unsatisfactory results that could be improved by individualized induction schemes and reducing the excessive psychological and financial burden of the couple.

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Conflicts of interest

There are no conflicts of interest.

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