Medical treatment of ovarian endometriomas: a prospective evaluation of the effect of dienogest on ovarian reserve, cyst diameter, and associated pain.

The aim of the present study was to evaluate the effect of medical treatment of ovarian endometriomas on cyst diameter, associated pain, and ovarian reserve as measured with antral follicle count (AFC) and anti-Mullerian hormone (AMH). In this prospective study, 32 patients with unilateral endometrioma associated with pelvic pain, underwent 6-month medical treatment with dienogest. Before treatment, and at the end of 6 months of treatment, patients underwent evaluation of endometrioma diameter and AFC at transvaginal ultrasonography, measurement of AMH, and evaluation of associated pain. Mean cyst diameter was 4.0 ± 1.3 cm at baseline, and 2.4 ± 1.2 cm after 6 months of treatment (p < .0001), for a reduction in diameter of 40% and a reduction in volume of 79%. Mean visual analog scale score at enrollment was 6.3 ± 2.0, with a significant improvement at 6 months (0.9 ± 1.0, p < .0001). AFC for the affected ovary improved from 4.2 ± 2.8 at baseline, to 8.6 ± 4.2 cm after 6 months (+105%; p < .0001). AMH did not change significantly from baseline (3.40 ± 2.32 ng/mL) to end of treatment (2.80 ± 1.90 ng/mL, -18%, p = .27). Medical treatment with dienogest significantly reduces endometrioma diameter and associated pain, whereas the ovarian reserve appears to be preserved, with a significant improvement of AFC and no significant change in AMH.

Ovarian Reserve Reduction With Surgery Is Not Correlated With the Amount of Ovarian Tissue Inadvertently Excised at Laparoscopic Surgery for Endometriomas.

The aim of the present study was to evaluate the effect of laparoscopic cystectomy on ovarian reserve by means of anti-Müllerian hormone (AMH) serial measurements and to compare AMH values with the number of inadvertently removed follicles in histological specimens. Fifty-two women were enrolled: 34 patients with endometriomas (group 1) and 18 patients with other benign ovarian cysts (group 2). All patients underwent laparoscopic cystectomy performed by a single experienced surgeon. The AMH was measured before, and 1, 3, and 6 months after cystectomy in group 1, and before and 6 months after surgery in group 2. Preoperative AMH levels (mean [standard deviation, SD]) in group 1 (3.39 [2.43] ng/mL) were not significantly different from group 2 (3.74 [2.57] ng/mL; P = .68). In group 1, a significant decrease in AMH levels of 43.4% was observed at 1 month (1.93 [1.36]; P = .003), and of 63.1% at 3 months (1.25 [1.00]; P = .007) postoperatively. The AMH increased not significantly between the third and sixth months in group 1 (+9.4%). Six months after surgery, AMH was reduced by 59.3% compared to baseline values in group 1 (P = .012), and by 29.5% in group 2 (P = .200). A significant difference in the AMH decrease was present between bilateral and monolateral endometriomas (P = .006). There was no correlation between the reduction rate of AMH and the number of follicles inadvertently removed in patients with endometriomas (P = .669). In conclusion, AMH decreases significantly after surgical excision of ovarian endometriomas. The postoperative decrease does not appear to correlate with the amount of ovarian tissue inadvertently excised with the endometrioma wall.

Management of endometriosis from diagnosis to treatment: roadmap for the future.

Endometriosis, in spite of decades of research on the topic, remains a mysterious and elusive disease. Both in the fields of diagnosis and treatment, many issues remain unresolved, and the scientific community strives in trying to find universal criteria for diagnosis, and algorithms of treatment that may be universally applied. Recently, there has been a shift away from the view of the need of invasive diagnosis and therapy with the universal use of laparoscopy. Today the diagnosis of endometriosis may be reliably performed with noninvasive methods, and therapy can be nonsurgical in most cases. Recent guidelines state that diagnostic laparoscopy may be better seen as a second line of investigation, whereas medical therapy with either oral estroprogestins or progestogens is the first therapeutic option in case of associated pain. A thorough discussion with the patient should address all the available treatments, so as to make a shared decision on which treatment best fits the needs of that single patient.

Antimüllerian hormone is reduced in the presence of ovarian endometriomas: a systematic review and meta-analysis.

OBJECTIVE: To evaluate if the presence of endometriomas impacts on the ovarian reserve as evaluated with antimüllerian hormone (AMH). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Patients with unoperated endometriomas versus controls without endometriomas. INTERVENTION(S): Electronic databases searched up to June 2017 to identify articles evaluating AMH levels in patients with unoperated endometriomas versus controls without endometriomas. MAIN OUTCOME MEASURE(S): The primary analysis was aimed at evaluation of AMH levels (mean and SD) in patients with and without endometriomas. Secondary analyses were aimed at evaluating AMH levels in patients with ovarian endometriomas compared to patients with either non-endometriosis benign ovarian cysts or healthy ovaries. RESULT(S): Of the 39 studies evaluated in detail, 17 were included, for a total of 968 patients with endometriomas and 1874 without endometriomas. AMH was significantly lower in patients with unoperated endometriomas compared to patients with no endometriomas (mean difference -0.84, with 95% confidence interval [CI] -1.16 to -0.52). At secondary analyses, AMH in patients with endometriomas was significantly lower both versus non-endometriosis benign ovarian cysts (mean difference -0.85, 95% CI -1.37 to -0.32, and versus women with healthy ovaries (mean difference -0.61, 95% CI -0.99 to -0.24). CONCLUSION(S): Ovarian reserve evaluated with AMH is reduced in patients with ovarian endometriomas compared both to patients with other benign ovarian cysts, and to patients with healthy ovaries.

Alpha lipoic acid in obstetrics and gynecology.

Alpha-Lipoic acid (ALA) is a natural antioxidant synthetized by plants and animals, identified as a catalytic agent for oxidative decarboxylation of pyruvate and α-ketoglutarate. In this review, we analyzed the action of ALA in gynecology and obstetrics focusing in particular on neuropathic pain and antioxidant and anti-inflammatory action. A comprehensive literature search was performed in PubMed and Cochrane Library for retrieving articles in English language on the antioxidant and anti-inflammatory effects of ALA in gynecological and obstetrical conditions. ALA reduces oxidative stress and insulin resistance in women with polycystic ovary syndrome (PCOS). The association of N-acetyl cysteine (NAC), alpha-lipoic acid (ALA), and bromelain (Br) is used for prevention and treatment of endometriosis. In association with omega-3 polyunsaturated fatty acids (n-3 PUFAs) with amitriptyline is used for treatment of vestibulodynia/painful bladder syndrome (VBD/PBS). A promising area of research is ALA supplementation in patients with threatened miscarriage to improve the subchorionic hematoma resorption. Furthermore, ALA could be used in prevention of diabetic embryopathy and premature rupture of fetal membranes induced by inflamation. In conclusion, ALA can be safely used for treatment of neuropatic pain and as a dietary support during pregnancy.

Current management of ovarian endometriomas.

The choice of treatment in case of ovarian endometriomas is one of the most discussed topics in Reproductive Medicine. Management options include expectancy, medical treatment, surgery, in vitro fertilization (IVF), or a combination of the above. The main presenting symptom, i.e. pain or infertility, usually guide the choice of treatment. Medical treatment is usually preferred as the first line option when pain is the associated symptom, whereas surgery or IVF are preferred in case of associated infertility. In most cases, however, the symptoms may overlap, and often a patient with infertility complains also of chronic pelvic pain, and vice versa. In addition, in many cases the patient may be asymptomatic, usually presenting with the incidental diagnosis of an ovarian endometrioma. Therefore, a strict categorization in two separate pathways of either associated pain or associated infertility, as the one outlined in current guidelines, may not represent the real clinical scenario. In this context, a personalized approach, taking into account several additional variables that are not considered in guidelines, is mandatory. In the present review, a symptom-driven approach to the management of ovarian endometriomas, that goes beyond the pain/infertility categorization, is described, considering additional parameters that guide the choice of treatment, with a patient-centered, personalized approach.

Management of Endometriomas.

Ovarian endometriomas affect 17 to 44% of women with endometriosis, and are often associated with pelvic pain and infertility. Treatment options include expectant management, medical and/or surgical treatment, and in vitro fertilization and embryo transfer (IVF-ET). The choice of treatment depends mostly on the associated symptoms. In most cases, surgery is the preferred choice, since endometriomas do not respond to medical treatment, which may only treat associated pain. In case of infertility, IVF-ET may be a suitable alternative to surgery, particularly when there is no associated pain. According to the best available scientific evidence, laparoscopic excision of the endometrioma wall should be considered the procedure of choice. Concerns have been raised as to the possibility that surgical excision may damage the ovarian reserve, but recent evidences demonstrate that part of the damage may be due to the presence of the endometrioma itself. Indication to surgical treatment should balance the possible risks of damaging the ovarian reserve with the advantages of surgery in terms of satisfactory pain relief rates and pregnancy rates, and of obtaining tissue specimen for ruling out the rare cases of unexpected ovarian malignancy. A score system to guide the clinician in the decision to perform or withhold surgery is presented.

Ovarian function during hormonal contraception assessed by endocrine and sonographic markers: a systematic review.

This systematic review focuses on the literature evidence for residual ovarian function during treatment with hormonal contraceptives. We reviewed all papers which assessed residual ovarian activity during hormonal contraceptive use, using endocrine markers such as serum anti-Müllerian hormone (AMH) concentrations, FSH, LH, oestradiol, progesterone and sonographic markers such as antral follicle count (AFC), ovarian volume and vascular indices. We considered every type (oestroprogestin or only progestin) and dosage of hormonal contraceptive and every mode of administration (oral, vaginal ring, implant, transdermal patch). We performed an electronic database search for papers published from 1 January 1990 until 30 November 2015 using PubMed and MEDLINE. We pre-selected 113 studies and judged 48 studies suitable for the review. Most studies showed that follicular development continues during treatment with hormonal contraceptives, and that during treatment there is a reduction in serum concentrations of FSH, LH and oestradiol, and also a reduction in endometrial thickness, ovarian volume and the number and size of antral follicles. The ovarian reserve parameters, namely AFC and ovarian volume, are lower among users than among non-users of hormonal contraception; regarding the effect of hormonal contraception on AMH, there are still controversies in the literature.

The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis.

STUDY QUESTION: Does surgical treatment of endometriomas impact on the ovarian reserve as evaluated with antral follicle count (AFC)? SUMMARY ANSWER: This meta-analysis of published data shows that surgery for endometrioma does not significantly affect ovarian reserve as evaluated by AFC. WHAT IS KNOWN ALREADY: Surgical excision of an ovarian endometrioma significantly affects ovarian reserve evaluated with anti-Mullerian hormone (AMH) levels. Data for other reliable markers of ovarian reserve, such as AFC, have not been pooled in meta-analyses. STUDY DESIGN, SIZE, DURATION: A systematic review with electronic searches of PubMed, MEDLINE and Embase up to April 2014 was conducted to identify articles evaluating AFC before and after surgery for ovarian endometriomas, or before or after surgery for the affected versus the contralateral ovary. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 24 studies evaluated in detail, 13 were included for data extraction and meta-analysis, including a total of 597 patients. The primary outcome at pooled analysis was AFC (mean and SD) for affected ovaries before and after surgery. Secondary outcomes were AFC for the affected ovary versus the contralateral ovary before surgery, and AFC for the operated versus the contralateral ovary after surgery. The data were pooled using the RevMan software by the Cochrane Collaboration. Heterogeneity between studies was based on the results of the χ(2) and I(2) statistics. A random-effect model was used for the meta-analysis because of high heterogeneity between studies. MAIN RESULTS AND THE ROLE OF CHANCE: AFC for the operated ovary did not change significantly after surgery (mean difference 0.10, 95% CI -1.45 to 1.65; P = 0.90). Lower AFC for the diseased ovary compared with the contralateral one was present before surgery, although the difference was not significant (mean difference -2.79, 95% CI -7.10 to 1.51; P = 0.20). After surgery, the operated ovary showed a significantly lower AFC compared with the contralateral ovary (mean difference -1.40, 95% CI -2.27 to -0.52; P = 0.002). LIMITATIONS, REASONS FOR CAUTION: Heterogeneity among the selected studies was high; therefore, limiting the conclusions of the present systematic review. WIDER IMPLICATIONS OF THE FINDINGS: Ovarian reserve evaluated with AFC is not reduced after surgical treatment of an endometrioma. A lower AFC is present for the affected ovary both before and after surgery. Recently, concerns have been raised as to the reliability of AMH as a marker of ovarian reserve. Based on the present findings, surgical treatment of an endometrioma may be considered safer for the ovarian reserve than previously thought. STUDY FUNDING/COMPETING INTERESTS: No external funding was sought or obtained for this study. No conflicts of interest are declared.

The uterine junctional zone: a 3-dimensional ultrasound study of patients with endometriosis.

OBJECTIVE: The uterine junctional zone (JZ) alterations are correlated with adenomyosis. An accurate evaluation of the JZ may be obtained by 3-dimensional transvaginal sonography (TVS). The aim of the present prospective study was to assess the value of detectable alterations by 3-dimensional TVS of the JZ in patients with pelvic endometriosis (diagnosed by laparoscopy and histologic condition) and to compare these findings with those of women without pelvic endometriosis. STUDY DESIGN: Eighty-two patients who were scheduled for laparoscopy had undergone previous surgery and 2- and 3-dimensional TVS. Uterine multiplanar sections that were obtained by 3-dimensional TVS were used to evaluate JZ features. During laparoscopy, an accurate staging of pelvic endometriosis was performed. JZ thickness and JZ alterations were correlated with stage of endometriosis. RESULTS: Of the 82 patients, 59 patients had endometriosis at laparoscopy and histology. The maximum thickness of JZ in patients with endometriosis was significantly greater than in patients without endometriosis (6.5 ± 1.9 mm vs 4.8 ± 1.0 mm; P < .001). The features of JZ appeared similar at different stages, whereas they are statistically different if correlated with patients without endometriosis. CONCLUSION: JZ thickness and its alterations are different in patients with endometriosis compared with those women without endometriosis and are not correlated with American Society of Reproductive Medicine staging methods. Because these JZ ultrasound features are associated mostly with adenomyosis, a correlation between endometriosis and JZ hyperplasia and adenomyosis could be hypothesized. Noninvasive evaluation of the JZ may be useful in the identification of those women who are affected by endometriosis also in early stage of the disease when there are no other sonographic signs of pelvic endometriosis.