Laparoscopic stripping of endometriomas negatively affects ovarian follicular reserve even if performed by experienced surgeons
Chiara Perono BiacchiardiLuisa Delle PianeMarco CamanniFrancesco DeltettoElena Maria DelpianoMarchino GlGianluca GennarelliAlberto Revelli
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Ovarian Reserve
Antral follicle
Anti-Müllerian hormone
Do infertile patients below the age of 40 years have a lower ovarian reserve, estimated by anti-Müllerian hormone (AMH) and total antral follicle count (AFC), than women of the same age with no history of infertility? Serum AMH and AFC were not lower in infertile patients aged 20–39 years compared with a control group of the same age with no history of infertility. The management of patients with a low ovarian reserve and a poor response to controlled ovarian stimulation (COS) remains a challenge in assisted reproductive technologies (ART). Both AMH levels and AFC reflect the ovarian reserve and are valuable predictors of the ovarian response to exogenous gonadotrophins. However, there is a large inter-individual variation in the age-related depletion of the ovarian reserve and a broad variability in the levels of AMH and AFC compatible with conception. Women with an early depletion of the ovarian reserve may experience infertility as a consequence of postponement of childbearing. Thus, low ovarian reserve is considered to be overrepresented among infertile patients. A prospective cohort study including 382 women with a male partner referred to fertility treatment at Rigshospitalet, Copenhagen, Denmark during 2011–2013 compared with a control group of 350 non-users of hormonal contraception with no history of infertility recruited during 2008–2010. Included patients and controls were aged 20–39 years. Women with polycystic ovary syndrome were excluded. On Cycle Days 2–5, AFC and ovarian volume were measured by transvaginal sonography, and serum levels of AMH, FSH and LH were assessed. Infertile patients had similar AMH levels (11%, 95% confidence interval (CI): −1;24%) and AFC (1%, 95% CI: −7;8%) compared with controls with no history of infertility in an age-adjusted linear regression analysis. The prevalence of very low AMH levels (<5 pmol/l) was similar in the two cohorts (age-adjusted odds ratio: 0.9, 95% CI: 0.5;1.7). The findings persisted after adjustment for smoking status, body mass index, gestational age at birth, previous conception and chronic disease in addition to age. The comparison of ovarian reserve parameters in women recruited at different time intervals could be a reason for caution. However, all women were examined at the same centre using the same sonographic algorithm and AMH immunoassay. This study indicates that the frequent observation of patients with a poor response to COS in ART may not be due to an overrepresentation of women with an early depletion of the ovarian reserve but rather a result of the expected age-related decline in fertility. The study received funding from MSD and the Interregional European Union (EU) projects 'ReproSund' and 'ReproHigh'. The authors have no conflict of interest. Not applicable.
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Endometriosis is a chronic disease mostly affecting women at reproductive age. There is a clear association between endometriosis and infertility; however, exact mechanisms are unknown. Some evidence suggests an adverse effect on oocytes. Endometriosis and its surgical treatment can affect quantitative ovarian reserve as well. In the presence of endometriomas, serum level of anti-Müllerian hormone (AMH) seems a more reliable marker of ovarian reserve than antral follicle count. Women with endometrioma have decreased serum AMH levels as compared with healthy controls. This is further declined after surgical excision, and the decline seems permanent. Bipolar cauterization of the ovary seems to be playing a role on ovarian damage. Extraovarian endometriosis and its surgical treatment can also be associated with decreased ovarian reserve, but there is limited information. Patients with endometriosis should be informed about fertility preservation options, especially in the presence of bilateral endometriomas or prior to surgery.
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Anti-Müllerian hormone
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The aim of the study was to study the influence of the ovarian endometrioma on the ovarian reserve, the ovarian response in ovarian hyperstimulation, and outcomes of assisted reproductive technologies (ART). Material and methods. The study included 43 infertility patients underwent the surgical treatment of an ovarian endometrioma in the history. During the study, the follicles were counted separately (according to transvaginal ultrasound), eggs and embryos were obtained from the operated and intact ovaries. Results. The number of follicles in the ovary, operated due to endometriosis, is significantly lower than in the contralateral ovary (p = 0.005). The number of ovules punctured from the ovary, operated for endometriosis, is less than the number of ovules obtained from the intact ovary, but the difference does not reach statistical significance (p = 0.07). The number of high-quality embryos obtained from the ovary, operated for endometrioma, is statistically significantly lower than the number of similar embryos obtained from the intact ovary (p = 0.013). Conclusion. According to the conducted study, it can be concluded that the surgical treatment of endometrioma in infertility patients with the need for the implementation of the reproductive function reduces the number of follicles in the operated ovary and, accordingly, does not lead to an improvement in indices of the infertility treatment using ART. At the same time, the very presence of endometrioma is also known to negatively impact on outcomes of ART. Therefore, in infertility patients with the reduced ovarian reserve, individualization of approaches to treatment is extremely important.
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Female infertility
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Ovarian Reserve (OR) is a term which describes the functional potential of the ovary, which constitutes the size of the ovarian follicle pool and reflects the number and quality of the oocytes which are within it. Assessment of the OR helps in reflecting the reproductive potential of women. Various markers are available for assessing the OR and the best marker is the Anti Mullerian Hormone (AMH) which reflects the ovarian follicular pool in the ovary. In this study, the serum level of AMH/MIS(Mullerian Inhibiting Substance)was estimated to assess the ovarian reserve in both fertile and infertile women.To assess the ovarian reserve in women of the fertile and subfertile groups with regular cycles, who were in the age range of 26 -33yrs, by estimating the level of AMH and those of other hormones like FSH and E2 and also to calculate the ovarian volume and the Antral follicular count by an ultrasonographic method.Thirty fertile and thirty sub fertile women whose ages ranged from 26-33yrs were included as group 1 and group 2 respectively. The hormones like AMH ,FSH and oestradiol were assayed. Measurement of the ovarian volume and the antral follicular count by doing a transvaginal ultrasonogram, was done in all the subjects who were involved in both the groups. The correlation test was studied between the variables and the test of significance of the variables between the 2 groups was also analyzed by the Statistical Package Of Social Sciences (SPSS).The Antral Follicular Count (AFC) and the ovarian volume were negatively correlated with the age. The ovarian volume was positively correlated with the AFC. The FSH negatively correlated with the AFC. The Anti Mullerian Hormone negatively correlated with the age, and it positively correlated with the AFC. The mean values of AFC, FSH, and AMH were also statistically significant between the two groups.AMH can be considered as a marker for assessing the ovarian reserve, as it is cycle independent as compared to the other hormones. The women in the subfertile group with low levels of AMH should be insisted to proceed for ART as early as possible.
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The study aim was to validate Beckman Coulter's fully automated Access Immunoassay System (BC Access assay) for anti-Müllerian hormone (AMH) and compare it with Beckman Coulter's Modified Manual Generation II assay (BC Mod Gen II), with regard to cycle AMH fluctuations and antral follicle counts.During one complete menstrual cycle, transvaginal ultrasound was performed on regularly menstruating women (n=39; 18-40years) every 2 days until the dominant ovarian follicle reached 16mm, then daily until observed ovulation; blood samples were collected throughout the cycle. Number and size of antral follicles was determined and AMH levels measured using both assays.AMH levels measured by the BC Access assay vary over ovulatory menstrual cycles, with a statistically significant pre-ovulatory decrease from -5 to +2 days around objective ovulation. Mean luteal AMH levels were significantly lower (-7.99%) than mean follicular levels but increased again towards the end of the luteal phase. Antral follicle count can be estimated from AMH (ng/mL, BC Access assay) concentrations on any follicular phase day. BC Access assay-obtained AMH values are considerably lower compared with the BC Mod Gen II assay (-19% on average); conversion equation: AMH BC Access (ng/mL)=0.85 [AMH BC Mod Gen II (ng/mL)]0.95.AMH levels vary throughout the cycle, independently of assay utilised. A formula can be used to convert BC Access assay-obtained AMH levels to BC Mod Gen II values. The number of antral follicles can be consistently estimated from pre-ovulatory AMH levels using either assay.
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To evaluate the relationship between endocrine ovarian reserve markers and antral follicle count (AFC) and ascertain which follicular cohort is most related to anti-Müllerian hormone (AMH), the best endocrine marker of quantitative ovarian reserve. We prospectively recruited 120 subjects with regular menstrual cycles undergoing IVF treatment. 3D TVS and venepuncture were performed in the early follicular phase (day 2–5) of the menstrual cycle. The number and size of each antral follicle was quantified using sono-automatic volume calculation. The follicles were sub-divided into cohorts according to their absolute size: < 2.0 mm, 2.0–3.0 mm, 3.1–4.0 mm, 4.1–5.0 mm, 5.1–6.0 mm, 6.1–7.0 mm, 7.1–8.0 mm, 8.1–9.0 mm and 9.1–10.0 mm. The relationship of each follicular cohort with AMH, inhibin-B, follicular stimulating hormone (FSH) and oestradiol levels was evaluated using Spearman's correlation coefficient (r). 7 subjects with follicles of > 20 mm were excluded leaving 113 for analysis. The median (range) age, AMH, inhibin-B, FSH and oestradiol levels were 35 (24–40) years, 1.3 (0.2–3.9) ng/ml, 49.4 (7-264) pg/ml, 6.8 (3.0–11.9) IU/L and 165 (42-373) pmol/L respectively. The median (range) total AFC was 12 (2–39). The total AFC was significantly correlated with serum AMH (r = 0.43; P < 0.001), but not with inhibin-B (r = 0.18), FSH (r = − 0.10) or oestradiol (r = − 0.06). Follicles measuring 2.0–3.0 mm, 3.1–4.0 mm, 4.1–5.0 mm and 5.1–6.0 mm were most significantly correlated with AMH (r = 0.30, 0.27, 0.30 and 0.41 respectively; P < 0.01). There was no relationship between serum AMH levels for follicles measuring < 2.0 mm or > 6.0 mm. The total AFC is significantly correlated with serum AMH levels but not with inhibin-B, FSH or oestradiol. The number of antral follicles measuring 2–6 mm is most closely related to AMH levels and this follicular cohort is most reflective of the quantitative status of ovarian reserve.
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(Abstracted from Hum Reprod 2016;31(5):1034–1045) The study investigates the extent to which poor response to ovarian stimulation in assisted reproductive technologies is associated with a lower ovarian reserve, estimated by serum concentrations of anti-müllerian hormone (AMH) and antral follicle count (AFC), in infertile patients when compared with women of same age with no history of infertility. A prospective cohort study of 382 infertile patients referred for fertility treatment at The Fertility Clinic, Rigshospitalet, at Copenhagen University Hospital between September 2011 and October 2013 were compared with a control group of 350 nonusers of hormonal contraception with no history of infertility between August 2008 and February 2010.
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