https://orcid.org/0000-0003-1549-1802
Abstract
Does unilateral oophorectomy modify the relationship between serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC)?
No altered ‘per-ovary’ and ‘per-follicle’ AMH production and antral follicle distribution was evident in unilaterally oophorectomized women compared to matched controls.
The age of menopause onset is relatively unchanged in patients having undergone unilateral oophorectomy. Mechanisms that occur to preserve and maintain ovarian function in this context remain to be elucidated.
Forty-one infertile women, with no polycystic ovary syndrome (PCOS) and no endometriosis, aged 19–42 years old, having undergone unilateral oophorectomy (One Ovary group; average time since surgery: 23.8 ± 2.2 months) were retrospectively age-matched (±1 year) with 205 infertile women having two intact ovaries and similar clinical features (Control group).
Serum AMH levels, 3–4 mm AFC, 5–12 mm AFC, and total AFC (3–12 mm) were assessed on cycle Day 3 in both groups. Hormonal and ultrasonographic measurements obtained from patients in the Control group (i.e. having two ovaries) were divided by two to be compared with measurements obtained from patients of the One Ovary group (i.e. having one single remaining ovary). To estimate per-follicle AMH production, we calculated the ratio between serum AMH levels over 3–4 mm AFC, 5–12 mm AFC, and total AFC (3–12 mm), and the strength of the correlation between serum AMH levels and total AFC. The main outcome measure was to assess Day 3 AMH/Day 3 AFC ratio and hormonal-follicular correlation.
As expected, before correction, mean serum AMH levels (1.46 ± 0.2 vs 2.77 ± 0.1 ng/ml, P < 0.001) and total AFC (7.3 ± 0.6 vs 15.1 ± 0.4 follicles, P < 0.0001) were lower in the One Ovary group compared to the Control group, respectively. Yet, after correction, per-ovary AMH levels (1.46 ± 0.2 vs 1.39 ± 0.1 ng/ml) and total AFC (7.3 ± 0.6 vs 7.5 ± 0.2 follicles) values were comparable between the two groups. Consistently, per-follicle AMH levels (3–4 mm, 5–12 mm, and total) were not significantly different between the two groups (0.39 ± 0.05 vs 0.37 ± 0.02 ng/ml/follicle; 0.69 ± 0.12 vs 0.59 ± 0.05 ng/ml/follicle, and 0.23 ± 0.03 vs 0.19 ± 0.01 ng/ml/follicle; respectively). In addition, the prevalence of 3–4 mm follicles was comparable between the two groups (66.7% for One Ovary group vs 58.8% for Control group, respectively). Finally, the correlation between serum AMH levels and total AFC was similar for patients in the One Ovary group (r = 0.70; P < 0.0001) compared to those in the Control group (r = 0.68; P < 0.0001).
The retrospective character of the analysis might lead to potential bias.
The present investigation did not provide evidence of altered ‘per-ovary’ and ‘per-follicle’ AMH production and antral follicle distribution in unilaterally oophorectomized women compared to matched controls. Further studies are warranted to support the hypothesis that follicle-sparing mechanisms are clearly at stake in remaining ovaries after unilateral oophorectomy to explain their long-lasting function and timely menopausal onset.
The authors have no funding or competing interests to declare.
N/A.
Introduction
Ovarian aging is a long and complex process characterized by the quantitative and qualitative attrition of ovarian follicles (Block, 1952; Gougeon, 1996; Broekmans et al., 2009). Previous studies have suggested that major folliculogenesis rearrangements occurred to preserve and maintain ovarian function. The decline of anti-Müllerian hormone (AMH) levels was reported to be slower in patients with low age-specific AMH levels at baseline compared to patients with high age-specific AMH levels (de Kat et al., 2016). Furthermore, although menopause onset could be expected to occur earlier after an abrupt depletion of the ovarian reserve, the difference of age at menopause onset between patients having undergone unilateral oophorectomy and patients with no history of unilateral oophorectomy is of only 1.1–1.2 years according to previous studies (Yasui et al., 2012; Bjelland et al., 2014). The fact that the age of menopause onset is relatively unchanged in patients having undergone unilateral oophorectomy (Faddy et al., 1992; Faddy and Gosden, 1995; McGee and Hsueh, 2000; Yasui et al., 2012; Bjelland et al., 2014) suggests the existence of mechanisms involved to maintain ovarian function in this context. Initial follicular recruitment might be slower in the remaining ovary, leading to fewer follicles initiating growth and to a smaller growing follicle mass.
The decline of the ovarian reserve is mainly attributed to the exhaustion of the pool of non-growing follicles (NGFs). Indeed, the pool of NGFs progressively decreases in time through mechanisms of recruitment, development into dominant follicle, ovulation, and atresia (Block, 1952; Gougeon and Chainy, 1987; Richardson et al., 1987; Faddy et al., 1992; Gougeon et al., 1994). A mathematical model suggested that the decline of NGFs might be bi-exponential, with an acceleration at the age of 37.5 years old, when approximately 25 000 NGFs are left (Faddy et al., 1992; Gougeon et al., 1994; Faddy and Gosden, 1995, 1996; Faddy, 2000). This increased depletion rate could be explained by an accelerated initiation of follicular growth during the pre-menopausal decade (Gougeon et al., 1994) and/or by increased follicular atresia at primordial stages (Faddy and Gosden, 1995). However, the accuracy of these models might be limited by the difficulty of correctly estimating the number of NGFs. Conversely, a more recent study performed with modern stereology techniques suggested that the rate of follicular loss constantly increased in time, with no sudden change of the number of NGFs (Hansen et al., 2008; Knowlton et al., 2014). This approach of ovarian decline is consistent with the fact that physiological aging processes tend to evolve gradually (Kirkwood, 1998; Leidy et al., 1998).
Altogether, precisely evaluating the ovarian reserve and the quickness of its decline remains a challenge. Although their performance is still a matter of debate (Bancsi et al., 2002; van Rooij et al., 2004; Grynberg et al., 2010a), hormonal parameters and small antral follicle count (AFC) measured by ultrasound scans have been suggested as efficient non-invasive methods to quantify the degree of follicular loss (Navot et al., 1987; Muasher et al., 1988; Fanchin et al., 1994; Licciardi et al., 1995; Seifer et al., 1997; Fanchin et al., 2003a). Furthermore, AMH, a glycoprotein belonging to the transforming growth factor-superfamily (Cate et al., 1986), has been described as the most reliable hormonal marker of the follicular stockpile in adults over the past decades (de Vet et al., 2002; Seifer et al., 2002; van Rooij et al., 2002; Kim et al., 2017). The production of AMH is FSH-independent, and occurs in granulosa cells of large primary follicles to early antral stage ovarian follicles (Durlinger et al., 2002a). Its age-related decline precedes the changes of traditional markers of ovarian reserve such as FSH, inhibin B and oestradiol (Fanchin et al., 2003b; Grynberg et al., 2010a,b). The histological examination of ovaries in 42 patients undergoing unilateral oophorectomy suggested that the number of primordial follicles were strongly correlated to serum AMH levels and AFC assessed 2 weeks before surgery (Hansen et al., 2011). Mean AMH levels measured in young girls after unilateral oophorectomy were 2.70 ± 2.11 ng/ml, and adult women with a history of unilateral oopherectomy were reported to have significantly lower AMH compared to controls(Rustamov et al., 2016; Oskayli et al., 2019). AMH may also have an important role in human folliculogenesis (Durlinger et al., 1999, 2002b; Weenen et al., 2004). In vivo and in vitro studies have described AMH as an inhibitor of the recruitment of primordial follicles into the pool of growing follicles and suggested that AMH may also decrease the responsiveness of growing follicles to FSH (Durlinger et al., 1999, 2001, 2002b). Hence, AMH may play a role in the intra-ovarian paracrine signaling of reproductive decline. Interestingly, AMH levels were reported to be increased in patients who had undergone oophorectomy at a late reproductive age (Wilkosz et al., 2014). Changes in per-ovary or per-follicle AMH production in patients having undergone unilateral oophorectomy might be a mechanism favoring follicle-sparing in these patients.
Altogether, mechanisms involved to maintain and preserve ovarian function after unilateral oophorectomy remain to be established. Per-ovary rearrangements of folliculogenesis might be at stake to preserve and maintain ovarian function. Since AMH is involved in the inhibition of initial follicular recruitment and is a reflection of the number of growing and non-growing follicles, AMH might also play a role in this context.
The aim of our study was to investigate whether per-ovary antral follicle count and distribution were altered, as well as whether per-ovary and per-follicle AMH production was increased, in unilaterally oophorectomized women.
Materials and methods
Subjects
Our study included 246 infertile women, aged 19–42 years old, undergoing routine explorations during spontaneous cycles in our center. Out of the 246 patients, 41 had a single remaining ovary as a result of unilateral oophorectomy (One Ovary group) and were retrospectively age-matched (± 1 year) with 205 women having both ovaries intact (Control group) and similar clinical features. Patients in both groups met the following inclusion criteria: (i) regular, ovulatory menstrual cycles of 25–35 days; (ii) no clinical signs of hyperandrogenism; (iii) no current or past disease affecting ovaries, or affecting gonadotropin/sex steroid secretion, clearance or excretion; (iv) no current hormone therapy; (v) correct visualization of ovary(ies) by transvaginal ultrasound scan; (vi) total number of small antral follicles (total AFC; 3–12 mm in diameter) between 1 and 24 follicles, including both ovaries when present; (vii) no current endometrioma. The study was approved by the Institutional Review Board of Antoine Béclère University Hospital.
Our analysis aimed at detecting per-ovary rearrangements of folliculogenesis. Hence, hormonal and ultrasonographic measurements obtained from patients in the Control group (i.e. having two ovaries) were divided by two to be compared with measurements obtained from patients of the One Ovary group (i.e. having one single remaining ovary).
Hormonal measurements and ultrasound scans
On cycle Day 3, each patient had a blood sample to measure AMH, estradiol (E2) and FSH levels and a transvaginal ultrasound scan to assess antral follicle count.
Serum AMH levels were determined using an ELISA (Beckman-Coulter, Villepinte, France). Intra- and inter-assay coefficients of variation were inferior to 6% and 10%, respectively. The minimal detection limit was 0.13 ng/ml, and linearity was up to 21 ng/ml. Serum levels of E2 and FSH were determined using an automated multi-analysis system with chemiluminescence detection (ACS-180; Bayer Diagnostics, Puteaux, France). For E2, measurements, functional sensitivity was of 15 pg/ml and intra-assay and inter-assay coefficients of variability (CV) were 8% and 9%, respectively. For FSH measurements, functional sensitivity was of 0.1 mIU/ml and intra-assay and inter-assay CV were 3% and 5%, respectively.
Ultrasound scans were performed by one single operator using a 3.7–9.3 MHz multi-frequency transvaginal probe (RIC5-9H, Voluson E8, General Electric Medical Systems, Paris, France). The operator was blinded to results of hormone assays. The number and size of small antral follicles were determined by ultrasound scan. Follicles with a mean diameter of 3–12 mm (mean of two orthogonal diameters) were considered. To obtain a higher image resolution quality and an optimal recognition of follicular borders, the ultrasound scanner included a tissue harmonic imaging system (Thomas and Rubin, 1998). Intra-analysis CV for follicular and ovarian measurements were <5% and their minimal detection limit was 0.1 mm.
Follicle distribution
To show a possible redistribution of antral follicles (3–12 mm in diameter) between patients with one remaining ovary after unilateral oophorectomy (One Ovary group) and patients with both ovaries intact (Control Group), follicles were classified into two categories according to diameter: 3–4 mm AFC and 5–12 mm AFC.
Per-follicle AMH production
Since AMH is produced by follicles, serum AMH levels are a result of AMH produced by each follicle individually and the total number of follicles. Hence, per-follicle AMH production was defined as the ratio between serum AMH levels and small antral follicle count (AMH/AFC). We calculated ratios between serum AMH levels over total AFC, 3–4 mm AFC, and 5–12 mm AFC.
Statistical analysis
Measures of central tendency and of variability used were mean and SE when data distribution was normal, and median and ranges when normality could not be ascertained. Differences between the two groups were evaluated with Student’s T or Mann–Whitney tests, when appropriate. Relationships between two different continuous variables were assessed by correlation. Fisher r to z-test was used to determine whether the coefficient of correlation (r) was significantly different from zero. Strengths of correlations were evaluated by comparing correlation coefficients using a test of ‘Appraisal of independent correlation coefficients’. P value <0.05 was considered statistically significant.
Results
Patient and follicle characteristics
Our study was composed of 246 patients (One Ovary group: n = 41; Control group: n = 205). Mean age was of 35.1 ± 0.3 years old. Indications of unilateral oophorectomy for patients in the One Ovary group were: endometriomas (n = 13); ovarian torsion (n = 12); borderline tumor (n = 9); or non-endometriotic cysts (n = 7). Average time between surgery and hormonal and follicular assessments was 23.8 ± 2.2 months.
Patients and follicle characteristics in the two groups are described Table I. As expected, before correction, mean serum AMH levels (1.46 ± 0.2 vs 2.77 ± 0.1 ng/ml, P < 0.001) and total AFC (7.3 ± 0.6 vs 15.1 ± 0.4 follicles, P < 0.0001) were lower in the One Ovary group compared to the Control group, respectively. Yet, after correction, per-ovary AMH (1.46 ± 0.2 vs 1.39 ± 0.1 ng/ml) and total AFC (7.3 ± 0.6 vs 7.5 ± 0.2 follicles) values were similar between the two groups. Serum E2 and FSH levels were significantly higher in the One Ovary compared to the Control group (45.2 ± 5.4 vs 35.3 ± 2.0, P < 0.05 and 9.0 ± 0.7 vs 7.0 ± 0.2, P < 0.0003, respectively).
Patient characteristics in the One Ovary group and Control group.
| One Ovary group | Control group | ||
|---|---|---|---|
| (n = 41) | (n = 205) | P-value | |
| Ages (years)a | 34.1 ± 0.6 | 35.2 ± 0.3 | NSb |
| Serum AMH (pg/ml)a | 1.46 ± 0.2 | 2.77 ± 0.1 | <0.001 |
| Corrected per-ovary serum AMH (pg/ml)a | 1.46 ± 0.2 | 1.39 ± 0.1 | NSb |
| No. of follicles 3-12 mma | 7.3 ± 0.6 | 15.1 ± 0.4 | <0.0001 |
| Corrected per-ovary no. of follicles 3–12 mma | 7.3 ± 0.6 | 7.5 ± 0.2 | NSb |
| Serum E2 levels (pg/ml)a | 45.2 ± 5.4 | 35.3 ± 2.0 | <0.05 |
| Serum FSH levels (mIU/ml)a | 9.0 ± 0.7 | 7.0 ± 0.2 | <0.0003 |
| One Ovary group | Control group | ||
|---|---|---|---|
| (n = 41) | (n = 205) | P-value | |
| Ages (years)a | 34.1 ± 0.6 | 35.2 ± 0.3 | NSb |
| Serum AMH (pg/ml)a | 1.46 ± 0.2 | 2.77 ± 0.1 | <0.001 |
| Corrected per-ovary serum AMH (pg/ml)a | 1.46 ± 0.2 | 1.39 ± 0.1 | NSb |
| No. of follicles 3-12 mma | 7.3 ± 0.6 | 15.1 ± 0.4 | <0.0001 |
| Corrected per-ovary no. of follicles 3–12 mma | 7.3 ± 0.6 | 7.5 ± 0.2 | NSb |
| Serum E2 levels (pg/ml)a | 45.2 ± 5.4 | 35.3 ± 2.0 | <0.05 |
| Serum FSH levels (mIU/ml)a | 9.0 ± 0.7 | 7.0 ± 0.2 | <0.0003 |
Means ± SE.
Not statistically significant.
AMH, anti-Müllerian hormone; E2, estradiol.
Patient characteristics in the One Ovary group and Control group.
| One Ovary group | Control group | ||
|---|---|---|---|
| (n = 41) | (n = 205) | P-value | |
| Ages (years)a | 34.1 ± 0.6 | 35.2 ± 0.3 | NSb |
| Serum AMH (pg/ml)a | 1.46 ± 0.2 | 2.77 ± 0.1 | <0.001 |
| Corrected per-ovary serum AMH (pg/ml)a | 1.46 ± 0.2 | 1.39 ± 0.1 | NSb |
| No. of follicles 3-12 mma | 7.3 ± 0.6 | 15.1 ± 0.4 | <0.0001 |
| Corrected per-ovary no. of follicles 3–12 mma | 7.3 ± 0.6 | 7.5 ± 0.2 | NSb |
| Serum E2 levels (pg/ml)a | 45.2 ± 5.4 | 35.3 ± 2.0 | <0.05 |
| Serum FSH levels (mIU/ml)a | 9.0 ± 0.7 | 7.0 ± 0.2 | <0.0003 |
| One Ovary group | Control group | ||
|---|---|---|---|
| (n = 41) | (n = 205) | P-value | |
| Ages (years)a | 34.1 ± 0.6 | 35.2 ± 0.3 | NSb |
| Serum AMH (pg/ml)a | 1.46 ± 0.2 | 2.77 ± 0.1 | <0.001 |
| Corrected per-ovary serum AMH (pg/ml)a | 1.46 ± 0.2 | 1.39 ± 0.1 | NSb |
| No. of follicles 3-12 mma | 7.3 ± 0.6 | 15.1 ± 0.4 | <0.0001 |
| Corrected per-ovary no. of follicles 3–12 mma | 7.3 ± 0.6 | 7.5 ± 0.2 | NSb |
| Serum E2 levels (pg/ml)a | 45.2 ± 5.4 | 35.3 ± 2.0 | <0.05 |
| Serum FSH levels (mIU/ml)a | 9.0 ± 0.7 | 7.0 ± 0.2 | <0.0003 |
Means ± SE.
Not statistically significant.
AMH, anti-Müllerian hormone; E2, estradiol.
Per-follicle AMH production and hormonal-follicular relationships
Per-follicle AMH levels (total, 3–4 mm, and 5–12 mm) were not significantly different between the two groups (0.22 ± 0.03 vs 0.17 ± 0.01 ng/ml/follicle, 0.39 ± 0.05 vs 0.37 ± 0.02 ng/ml/follicle, and 0.69 ± 0.12 vs 0.59 ± 0.05 ng/ml/follicle, respectively). Moreover, the prevalence of 3–4 mm follicles was comparable between the One Ovary group and Control group (66.7% vs 58.8%, respectively) (Fig. 1).
Antral follicle distribution in the One Ovary (red) and control (black) groups. Lower line: first quartile (Q1); middle line: median; upper line: third quartile (Q3) Bar: minimum value to maximum value. Points: outliers.
The strong correlation between serum AMH levels and total AFC was unaffected in patients in the One Ovary group (r = 0.70; P < 0.0001) compared to the Control group (r = 0.68; P < 0.0001) (Fig. 2). In addition, while serum E2 levels failed to correlate with AFC in both groups, a significant inverse correlation was observed between FSH levels and AFC in patients unilaterally oophorectomized (r=−0.14; P < 0.05) and in the control (r=−0.39; P < 0.0001) group. The strength of hormonal-follicular relationships in both groups is displayed in Table II. As shown, the intensity of the relationships (r values) between the total number of 3–12 mm follicles and serum AMH levels did not differ, irrespectively of the presence of one or two ovaries. However, the strength of the relationship between FSH and antral follicle counts was significantly decreased by unilateral oophorectomy (P < 0.02).
Strengths of hormonal-follicular relationships in the One Ovary group and Control group.
| Correlation coefficients (r) | |||
|---|---|---|---|
| One Ovary group (n = 41) | Control group (n = 205) | P-value | |
| No. of follicles (3–12 mm) × serum AMH levels | 0.70 | 0.68 | NSa |
| No. of follicles (3–12 mm) × serum E2 levels | −0.18 | −0.02 | NSa |
| No. of follicles (3–12 mm) × serum FSH levels | −0.14 | −0.39 | <0.02 |
| Correlation coefficients (r) | |||
|---|---|---|---|
| One Ovary group (n = 41) | Control group (n = 205) | P-value | |
| No. of follicles (3–12 mm) × serum AMH levels | 0.70 | 0.68 | NSa |
| No. of follicles (3–12 mm) × serum E2 levels | −0.18 | −0.02 | NSa |
| No. of follicles (3–12 mm) × serum FSH levels | −0.14 | −0.39 | <0.02 |
Not statistically significant.
Strengths of hormonal-follicular relationships in the One Ovary group and Control group.
| Correlation coefficients (r) | |||
|---|---|---|---|
| One Ovary group (n = 41) | Control group (n = 205) | P-value | |
| No. of follicles (3–12 mm) × serum AMH levels | 0.70 | 0.68 | NSa |
| No. of follicles (3–12 mm) × serum E2 levels | −0.18 | −0.02 | NSa |
| No. of follicles (3–12 mm) × serum FSH levels | −0.14 | −0.39 | <0.02 |
| Correlation coefficients (r) | |||
|---|---|---|---|
| One Ovary group (n = 41) | Control group (n = 205) | P-value | |
| No. of follicles (3–12 mm) × serum AMH levels | 0.70 | 0.68 | NSa |
| No. of follicles (3–12 mm) × serum E2 levels | −0.18 | −0.02 | NSa |
| No. of follicles (3–12 mm) × serum FSH levels | −0.14 | −0.39 | <0.02 |
Not statistically significant.
Relationships between serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) in the One ovary (red symbols) and Control (black symbols) groups. P < 0.0001, statistically significant.
Discussion
The present study was designed to investigate the effect of unilateral oophorectomy on hormonal markers of ovarian follicular status and on the number and distribution of antral follicles measured on cycle Day 3. Previous works using animal or mathematical models have suggested that patients having undergone unilateral oophorectomy early in life did not have advanced menopause onset (Danforth et al., 1989). Although the precise underlying mechanisms remain ill established, initial follicular recruitment is thought to be slower in the remaining ovary, leading to a lower number of follicles initiating growth and to a smaller growing follicle mass. Hence, we performed an extensive hormonal and follicular evaluation comparing patients having a single remaining ovary after unilateral oophorectomy and controls having both ovaries intact. Although it is possible that women of the Control group might have an altered ovarian reserve compared to global population, we aimed to select all women included in our study among women undergoing routine explorations during spontaneous cycles. Our results showed that the strength of the correlation between serum AMH levels and AFC was not modified by unilateral oophorectomy. Furthermore, serum AMH levels have been reported to be strongly related to early AFC, with a relationship that is remarkably more intense than with other classical hormonal markers of follicular status and development (de Vet et al., 2002; Fanchin et al., 2003b). Consistently, in our study, patients with a history of unilateral oophorectomy having a lower AFC compared to women with two intact ovaries had lower serum AMH levels. As expected, although serum FSH levels remained conversely correlated to AFC in both groups, the strength of the correlation was significantly decreased after unilateral oophorectomy, most probably as a consequence of the presence of overdeveloped follicles (Grynberg et al., 2010b). Moreover, our analysis aimed at detecting per-ovary rearrangements of folliculogenesis and their possible relationship with AMH. Since they tend to produce more AMH, follicles with a diameter of less than 4 mm were evaluated separately (Weenen et al., 2004). We analyzed two groups of antral follicles (3–4 mm and 5–12 mm in diameter) according to their capacity to produce AMH. Our results failed to find any follicular redistribution in women with a single remaining ovary. Several lines of evidence indicate that AMH may be a key actor in human folliculogenesis by regulating primordial follicle activation (Durlinger et al., 1999, 2002a; Weenen et al., 2004). Indeed, in vitro studies using knock-out models in rodents reported that ovaries of Amh–/– mice showed significant ovarian depletion by 4 months of age despite an initial normal-sized primordial follicular pool (Durlinger et al., 1999). In addition, the total number of follicles of Amh+/– (i.e., heterozygous) females ranged between that of Amh+/+ and Amh–/– females, suggesting that AMH inhibits primordial follicle recruitment in a dose-dependent manner (Durlinger et al., 1999). In vitro culture studies performed both on rodents and humans were in line with in vivo results showing that AMH inhibits the transition from primordial to primary follicles (Durlinger et al., 2002a,b; Carlsson et al., 2006; Nilsson et al., 2007). However, because primordial follicles are devoid of AMH receptor, mechanisms by which AMH suppresses follicular activation remain to be established. Most in vitro and in vivo experiments suggested that AMH produced by growing follicles may act as a negative paracrine feedback signal on neighboring primordial follicles to inhibit their recruitment. A retrospective analysis (Wilkosz et al., 2014) suggested that in case of unilateral oophorectomy performed at a late reproductive age, there was a shift in the proportion of resting follicles entering the growing cohort, associated with increased AMH levels. This phenomenon could possibly explain the maintenance of ovarian function in this context. Hence, given that serum AMH levels reflect the number of growing and non-growing follicles, we investigated whether per-follicle AMH production was altered in unilaterally oophorectomized patients. To clarify this issue, we extrapolated per-follicle AMH production from the ratio between serum AMH levels and AFC. Although this parameter does not include follicles that are undetectable by ultrasound scan (Fanchin et al., 2005), it has been shown to be reliable in the predictability of IVF with embryo transfer (IVF-ET) outcome, thus opening new perspectives in the interpretation of serum AMH levels and reproductive competence of ovarian follicles. The present data failed to show an alteration of per-follicle AMH levels (total, 3–4 mm, and 5–12 mm) in unilaterally oophorectomized women compared to control patients.
In conclusion, the present investigation did not provide evidence of altered ‘per-ovary’ and ‘per-follicle’ AMH production and antral follicle distribution in unilaterally oophorectomized women compared to matched controls, which is inconsistent with the presumable implication of AMH in the mechanisms driving follicle loss in the remaining ovary. Further studies are warranted to determine the precise follicle-sparing mechanisms at stake in these remaining ovaries to explain their long-lasting function and timely menopausal onset.
Data availability
The data underlying this article will be shared on reasonable request to the corresponding author.
Authors’ roles
Wrote the paper: M.G. and J.L. Proofread English text: J.L. Conceived and designed the study: M.G. and C.S. Analyzed the data: M.G. Contributed to materials/analysis tools: M.G., B.B.S., C.S. and C.S.
Funding
The authors have no funding source to declare.
Conflict of interest
The authors have no conflict of interest to declare.
References
