Treatment Of Endometriosis-associated Infertility Research Articles

Эффективность комбинированной терапии комплексом противомикробных пептидов и цитокинов и природным антикоагулянтом прямого действия у пациенток с эндометриальным бесплодием: первые результаты сравнительного исследования

Aim: to evaluate the efficacy concerning the combined use of a complex including antimicrobial peptides and cytokines and a natural direct oral anticoagulant in female patients with endometriosis-associated infertility in the setting of thin endometrium Patients and Methods: the article presents a conducted comparative study. The main group (n=25) included therapeutic and restorative measures using a drug containing the complex of antimicrobial peptides and cytokines (vaginal suppositories 25U vaginally and rectally, alternating, for 40 days) in combination with natural direct oral anticoagulant (2 capsules per os, 3 times daily, for 20 days). Before the therapy initiation and 3 menstrual cycles after the treatment, biomarker levels in menstruation (proinflammatory cytokine IL-6), endometrial thickness (endometrial echo parameter) were measured in the main group, where its echostructure, hysteroscopy and optical spectroscopy data were also evaluated. The follow-up was lasting for 6 months after the treatment. The analysis and comparison of reproductive outcomes were conducted in the main group receiving the studied drugs and in the retrospective comparison group (n=56), which received traditional cyclic hormone therapy and a course of systemic magnet therapy Results: after the treatment course in the main group, there was a tendency to the IL-6 increase in menstrualtion, an increase in endometrial thickness (endometrial echo) to optimal values, as well as an increase in the parameters of endometrial oxygen consumption and its proliferative ability according to optical spectroscopy. In the main group who received the studied drugs, pregnancy occurred in 44±7.9% of cases, whereas in the comparison group — in 38±5.9% (p=0.2). Conclusion: the article has shown the combined use efficacy of drugs with antimicrobial peptides, cytokines and the natural direct oral anticoagulant in the treatment of endometriosis-associated infertility in the setting of thin endometrium. An increase in the IL-6 level in menstruation of the main group may indicate an inflammatory response activation from the endometrium ("cure through exacerbation"). It is necessary to continue research with a larger sample of patients and an assessment of additional parameters (microcirculation, tissue sensitivity) that characterize other links in the pathogenesis of endometriosis KEYWORDS: thin endometrium, endometriosis-associated infertility, menstruation biomarkers, diagnostic ultrasound, optical spectroscopy, complex of antimicrobial peptides and cytokines, natural direct oral anticoagulants. FOR CITATION: Motovilova T.M., Simakova V.Yu., Kachalina T.S., Borovkova L.V., Ponomareva I.V., Martiantseva I.V., Kruglova I.A., Lazukin V.F., Bogomolova M.D., Kazarinova D.A. The effectiveness of combination therapy with a complex of antimicrobial peptides and cytokines and a natural direct-acting anticoagulant in patients with endometrial infertility: first results of a comparative study. Russian Journal of Woman and Child Health. 2024;7(2):155–162 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-11.

The treatment of endometriosis-associated infertility: Erratum.

The treatment of endometriosis-associated infertility: Erratum.

The treatment of endometriosis-associated infertility.

To review the recent evidence around the treatment of infertility in patients with endometriosis. The management of endometriosis associated infertility remains challenging. There have been an increasing number of prospective observational studies highlighting the role of surgery to enhance assisted conception amongst those with deep rectovaginal endometriosis. Further validation studies confirm the role of the endometriosis fertility index in prediction of reproductive outcomes after surgery, and confirm that it can be employed in counselling patients prior to surgery on their likelihood of spontaneous conception. Further randomized trials are required to establish the role of surgically treating superficial and deep endometriosis and both spontaneous and assisted conception outcomes. Endometriosis continues to present challenges in counselling patients with regards to their fertility prospects. This article reviews the recent research findings that may assist in the management of patients with endometriosis associated infertility.

PREDICTION OF PREGNANCY ONSET IN THE TREATMENT OF ENDOMETRIOSIS ASSOCIATED INFERTILITY

The main data, that can predict the onset of pregnancy in the treatment of endometriosisassociated infertility, based on a literature review, are cited in the article. The articledescribes the principle methods for endometriosis- associated infertility treatment bymeans of laparoscopic surgery, subsidiary reproductive technologies, classifications ofendometriosis that can predict the onset of pregnancy.Objective – to analyze modern classifications of endometriosis, which can be used topredict the onset of pregnancy in endometriosis- associated infertility.Conclusion. The cited literature review certifies that prediction of the pregnancy onsetin patients with endometriosis- associated infertility remains to be a difficult task andconfirms expediency of the optimal variant search.

Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies.

Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better understanding of the pathogenesis of endometriosis-associated infertility is crucial for improving infertility treatment outcomes. Current theories regarding how endometriosis reduces fertility include anatomical distortion, ovulatory dysfunction, and niche inflammation-associated peritoneal or implantation defects. This review will survey the latest evidence on the role of inflammatory niche in the peritoneal cavity, ovaries, and uterus of endometriosis patients. Nonhormone treatment strategies that target these inflammation processes are also included. Furthermore, mesenchymal stem cell-based therapies are highlighted for potential endometriosis treatment because of their immunomodulatory effects and tropism toward inflamed lesion foci. Potential applications of stem cell therapy in treatment of endometriosis-associated infertility in particular for safety and efficacy are discussed.

Ovarian endometriosis and fertility preservation: a challenge in 2018.

Endometriosis is a benign, estrogen-dependent gynecological disorder. It is now well established that three different forms of endometriosis can occur in the pelvic cavity, namely peritoneal endometriosis, ovarian endometriosis and deep endometriotic nodules of the rectovaginal septum. Treatment of endometriosis-associated infertility has been investigated using both medical and surgical modalities. Surgery for ovarian endometriosis can lead to premature ovarian insufficiency (POI) and further infertility, so one of the most important goals of therapy should be preserving fertility. Procedures combining stripping and ablation should be considered the first-line approach for ovarian endometrioma-related infertility, in order to protect the ovarian reserve, which may already be depleted even before surgery. Autotransplantation of ovarian tissue should be considered in case of mandatory radical treatment (oophorectomy), or if conservative treatment poses a risk. For patients at risk of POI, particularly those undergoing gonadotoxic treatment, two main fertility preservation options exist: oocyte vitrification or reimplantation of fresh or frozen ovarian tissue. Both have advantages and disadvantages.

Selection of key recommendations for the management of women with endometriosis by an international panel of patients and professionals.

Can the differences in patients' and professionals' perspective regarding essential endometriosis care be accommodated in one set of key recommendations? Consensus between patients and professions on a key set of recommendations for essential endometriosis care was achieved. Guideline development alone will not lead to healthcare improvement. Quality indicators are needed to monitor actual care and guideline adherence. These can help with better implementation of the ESHRE guidelines in European hospitals and thereby improve the quality of endometriosis care. The first step in the development of quality indicators is to select a compact set of key recommendations. Using a RAND modified Delphi method, this study reports the systematic selection of key recommendations based on the ESHRE guideline 'Management of Women with Endometriosis' by an international expert panel of both patients and professionals during the study period of September 2015 and December 2015. An international panel of patients (n = 10) and medical professionals (n = 11) rated and prioritized the 83 recommendations extracted from the ESHRE guideline for relevance in three rounds. A strict consensus methodology was used to select key recommendations. The main outcome measure was one set of key recommendations for endometriosis care. A representative set of 17 key recommendations was selected from the preliminary set of 83 recommendations. This selection covers all dimensions of endometriosis care, including diagnosis, treatment of endometriosis-associated pain, treatment of endometriosis-associated infertility and miscellaneous topics such as prevention, menopause and relationship with cancer. Of the 21 experts, 17 participated in at least one round while 16 (76.2%) participated in all 3 rounds. The feasibility of the selected key recommendations was not assessed in this study. As not all panel members took part in all three rounds, some response bias may have occurred. This set of key recommendations is the first step in the development of quality indicators for monitoring and improving endometriosis care. The set is generic and can be used in hospitals internationally. A practice test should be conducted to assess the feasibility of our key recommendations in clinical practice. No funding was received for the conduct of this study. Members of the EndoKey study group did not receive payment. The authors and members of the EndoKey study group have no conflict of interest.

A Comparative Study of the use of Different Energy Sources in Laparoscopic Management of Endometriosis-Associated Infertility

Background: Although there is controversy about the mechanism by which endometriosis causes infertility, laparoscopic treatment for endometriosis-associated infertility is becoming popular. However, the optimal modality of energy sources used for dissection and ablation in infertile women remains unexplored. Objective: To study the best available evidence exploring the use of laparoscopic surgery in infertile women with endometriosis, compare various available energy sources, and their effect on surgical outcome and probability of pregnancy. Methods: A retrospective review of literature was done to explore the role of laparoscopic surgery and various energy sources in managing endometriosis-associated infertility, using keywords—endometriosis, laparoscopy, infertility, electrosurgery and ultrasonic energy. Results: Laparoscopic treatment of endometriosis using mechanical or electrical technologies was proposed in the 1980s. Later, use of lasers to vaporize endometriosis and to excise adhesions became popular. The invention of ultrasonic generator and tissue response electrosurgical generator has revolutionized laparoscopic surgery for endometriosis. Conclusion: No prospective randomized double-blind controlled trial has been conducted to date in this area. Current evidence suggests that laparoscopic excision or ablation, either by electrocautery or laser, improves pregnancy rates. However, the impact of newer energy sources and tissue dissection techniques in this field is yet to be explored.

Laparoscopic surgery for endometriosis-associated infertility: a pathophysiologic approach

Endometriosis has been one of the most confusing gynecological diseases since it was first described. Whereas there is a reasonable body of evidence in literature to demonstrate an association between endometriosis and infertility, a definite cause and effect relationship has not been established. The mechanism by which endometriosis causes infertility remains an enigma. Virtually every aspect of reproduction in women with endometriosis has been investigated and purported to be impaired. Impairment of implantation and pregnancy rates seems to affect women with endometriosis. Whether this is due to poor quality embryos derived from impaired oocytes or endometrial defects or both has been argued. Structural abnormalities of the uterine wall and tube in women with endometriosis have also been described by other researchers. Adding more confusion to this topic is the altered immune function and the peritoneal environment and their detrimental effects on the sperm motility and morphology. This uncertain pathophysiology has resulted in the lack of consensus on the treatment of endometriosis-associated infertility. The aim of this review is to describe the current pathophysiology of endometriosis-related infertility, how laparoscopic surgery may influence fertility rates.

The use and effectiveness of in vitro fertilization in women with endometriosis: the surgeon's perspective

To assess the use and effectiveness of IVF in a cohort of women undergoing surgery for endometriosis. Cohort study. University hospital. Four hundred thirty-eight patients who attempted to become pregnant after conservative surgery for endometriosis. Interview. Pregnancy and IVF use. One hundred ninety-four women conceived in vivo (44%). One hundred twenty-four women did not undergo IVF despite their infertility status (51% of the group of women who failed to conceive in vivo). One hundred thirty-nine women underwent at least one IVF attempt. The cumulative rate of IVF use at 36 months of infertility was 33%. The live-birth/ongoing pregnancy rate per started cycle and per patient was 10% and 20%, respectively. In a large tertiary care and referral center, IVF played only a minor role in the treatment of endometriosis-associated infertility.

Endometriose: Bewährte und innovative Therapiestrategien bei Schmerzen und Infertilität

The treatment of endometriosis focuses upon two main goals: the reduction of pain and the therapy of infertility. The treatment of pain associated with endometriosis has been well investigated. All major medical therapies proved to be better than placebo treatment. Comparing progesterone, oral contraceptives, GnRH analogs and danazol, no single treatment modality seems to be superior to the others. A marked reduction of endometriosis-associated pain can also be reached by the insertion of a levonorgestrel-releasing intrauterine system. A surgical procedure seems to be effective for the treatment of pain; however, the rate of recurrence is high. Other patients suffer from pain as a consequence of postoperative adhesion formation. The treatment of endometriosis-associated infertility is debated in the international literature: most authors reported that medical treatment does not improve fertility in endometriosis patients. In addition, however, new studies demonstrated the benefit of GnRH analogs for 3 to 6 months after surgery for the outcome of ART. The fertility of endometriosis patients can be improved by surgical procedures in severe endometriosis. The methods of assisted reproduction with ovarian stimulation, intrauterine insemination or IVF are successful, but to a lower extent compared to infertile patients without endometriosis. Especially for endometriosis patients, IVF has higher success rates compared to insemination. The affected patient and her physician should discuss possible treatment options and chose the therapy which improves her complaints, keeping in mind her reproductive wishes. In addition, we describe several innovative, not yet established, approaches in endometriosis treatment.

Endometriosis and assisted reproductive technologies.

The association between endometriosis and infertility is well established, and different mechanisms have been postulated to cause infertility depending on the stage of endometriosis. Controlled ovarian hyperstimulation improves pregnancy outcome for minimal to mild endometriosis; however, there are no randomized controlled studies of this technique in patients with severe disease. Further, ART appears to have an overall beneficial effect for all stages of endometriosis. Based on the current staging system, several studies have not been able to demonstrate a significant difference in true outcomes for different stages of the disease. The limitations of these studies have been discussed above. Similarly, the effect of endometriomas when considered independent of the stage is still unclear. In addition to ART, pretreatment with GnRH analogues or surgical intervention may be beneficial and needs to be addressed in randomized controlled studies. It is evident that we urgently need large randomized studies to answer several questions about the treatment of endometriosis-associated infertility with ART. Although our current practice is based primarily on retrospective observational studies and small randomized studies, the overall impact on pregnancy outcome is beneficial.

Treatment of endometriosis-associated infertility.

The choice of treatment options for endometriosis-associated infertility has been both controversial and complex, largely because of lack of data. In the last 10 years, better data from numerous studies with improved design support laparoscopic ablation and/or resection of lesions as the most successful for both minimal/mild and moderate/severe/extensive disease. Laparotomy should be performed when necessary. Observation alone is sometimes indicated in young women with minimal/mild disease. Hormonal suppression has no identifiable role, except perhaps for severe/extensive disease, before IVF or GIFT. Ovarian stimulation with clomiphene or gonadotropins and concomitant intrauterine insemination is indicated for minimal/mild disease. IVF and GIFT are often best for those who have failed other treatments, have advanced age, prolonged infertility, and/or multiple-factor infertility.

MANAGEMENT OF ENDOMETRIOSIS IN WOMEN OLDER THAN 40 YEARS OF AGE

Endometriosis in women older than 40 years of age presents unique therapeutic challenges to the practicing physician. Management requires the evaluation of reproductive goals and a determination of the objectives of therapy, including symptomatic relief and avoidance or delay of recurrence of disease. Important considerations in this age group include diminished fertility and impending menopause. The diagnosis and treatment for endometriosis-associated infertility must be undertaken in an expedient manner. Assisted reproductive technologies may be effective therapies for these patients. Conservative surgery may be necessary to preserve reproductive potential, but definitive surgery may be indicated in women with long-standing pelvic pain. Estrogen replacement therapy may be used in menopausal women with a history of endometriosis.

A comparison of ovulation suppression and ovulation stimulation in the treatment of endometriosis-associated infertility

This study compares ovulation stimulation or suppression with the pregnancy rate among infertile couples with endometriosis. The design is a nonrandomized, prospective, multicentered cohort analytic study. Two hundred and ninety-seven couples with laparoscopy-proven endometriosis were analyzed: 68 received no therapy, 42 received clomiphene and 74 received danazol. Forty patients (22%) conceived and pregnancy rates were similar in each treatment group. The relative likelihood of pregnancy associated with clomiphene was 2.9 (95% confidence limits 1.2–7.1); the relative likelihood of pregnancy with danazol was 1.02 (95% confidence limits 0.5–2.3). This study suggests that pregnancy rates during clomiphene treatment could be superior to expectant therapy, while pregnancy rate after danazol is similar to no treatment.

KTP/532 laser laparoscopy in the treatment of endometriosis-associated infertility

To determine the clinical effectiveness of the KTP/532 laser in treating endometriosis-associated infertility and to analyze the impact of additional infertility factors on outcome. Prospective cohort analysis of 74 consecutive patients followed up to 24 months after surgery. Tertiary institutional infertility clinic. Cumulative pregnancy rates (PRs), monthly fecundity rates, monthly probability of pregnancy, crude PRs, and cure rates. Thirty-eight percent (28) of patients conceived with a mean +/- SE time to conception of 7.2 +/- 0.8 months. The cure rates were 74% for the total patient sample, 51% for stage I, 69% for stage II, and 64% for stage III disease. Patients who had a cervical factor (P = 0.05), who underwent intrauterine insemination (P = 0.03), who received human menopausal gonadotropin (P = 0.03), or who had additional infertility factors (P = 0.02) had significantly lower crude PRs. The presence of additional infertility factors (P less than 0.02) and intrafimbrial adhesions (P less than 0.01) had a significant impact on cure rates. In the absence of additional factors, 60% (12) of patients with stage I and II conceived. When additional factors were excluded, the overall cure rate was 80%. The results indicate that the KTP/532 laser is an effective tool for the treatment of endometriosis-related infertility. The high prevalence of subtle adhesions may lend further impetus to operative laparoscopy for stage I and II disease. Additional infertility factors may adversely affect outcome.

Buserelin versus danazol in the treatment of endometriosis-associated infertility

A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated randomly to two treatment groups, one of which (32 patients) received oral danazol 600 μg/day and the other (30 patients) received intranasal buserelin 1200 μg/day for 6 months. Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment. Pain symptoms improved markedly during treatment in both groups. At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it (12 in the buserelin group and 13 in the danazol group), and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants. All of the patients were followed up for at least 12 months, during which pregnancy was attempted. At 18 months the cumulative pregnancy rate was 48% in the patients treated with buserelin and 43% in those treated with danazol. Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension. The side effects were more frequent and more severe in the danazol-treated patients, whereas those given buserelin generally reported only symptoms of hypoestrogenism. The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility, and its side effects are less severe.