A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

OBJECTIVE: The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. METHODS: Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. RESULTS: One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding (p < .005), easy bruising (p = .028), fissures (p = .008), petechiae/splinter hemorrhages (p < .001), and bleeding/blistering or open sores (p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum (p = .013) and the perianal region (p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population (p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population (p = .047). CONCLUSIONS: Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

Beyond vulvodynia: from a correct diagnosis to a multidisciplinary care program. A referral center experience.

BACKGROUND: Vulvodynia is a chronic pain condition without an identifiable cause. As such, it is a diagnosis of exclusion, and all other causes of vulvar pain should be excluded. Although a standard treatment for vulvodynia has not been established yet, multidisciplinary care programs appear to be effective. PUROPOSE: The aim of this retrospective monocentric study was to analyze the prevalence of vulvodynia among women referred to our institution for a suspected diagnosis and to evaluate the efficacy of a multidimensional treatment plan. The primary outcome was the prevalence of vulvodynia following differential diagnosis. Secondary outcomes included: prevalence of the differential diagnoses, symptom resolution rate following treatment, and the relation between persistence of symptoms and (a) patients' age; (b) coexisting chronic overlapping pain conditions (COPCs). RESULTS: After having ruled out all other causes of vulvar pain, only 40.1% of women were considered as affected by vulvodynia. The most frequent differential diagnoses included lower genital tract infections (25.3%), vulvar lichen sclerosus (17.6%) and vulvovaginal atrophy (8.2%). Following a multidisciplinary care program, resolution of symptoms was observed in 13.6% cases, improvement in 64.3% and persistence in 21.9%. We did not find a statistically significant association between persistence of symptoms and age > 38 years (OR 2.10; p = 0.30). Women with one or more COPCs other than vulvodynia had a 75% increased risk of not obtaining a resolution of symptoms (OR 1.75; p = 0.44). CONCLUSION: A thorough differential diagnosis and a multidisciplinary care program may represent a first way out of the muddle in the management of these patients.

Is there a role for platelet rich plasma injection in vulvar lichen sclerosus? A self-controlled pilot study.

BACKGROUND: Owing to the evidence that as many as 30-40% of patients with vulvar lichen sclerosus (VLS) fail to report a remission of symptoms with first-line corticosteroid treatment (TCS), especially as what regards dyspareunia, we aimed to analyze patients' satisfaction following vulvar injection of autologous platelet-rich plasma (PRP). This is intended as an adjunctive treatment, to be used following TCS, and appears to promote tissue repair. It may also possibly have immunomodulatory proprieties. MATERIALS AND METHODS: Patients with VLS were considered eligible for this pilot study if, despite having been treated with a 3-month TCS regimen, they reported a persistence of symptoms. PRP was produced in a referral center using a manual method and a standardized protocol. Each patient received three treatments 4 to 6 weeks apart. RESULTS: A total of 50 patients with a median age of 53 years [IQR 38-59 years] were included in the study. 6 months after the last injection of PRP all patients were either satisfied or very satisfied with the treatment (100%; 95% CI 93-100%). Median NRS scores for itching, burning, dyspareunia and dysuria were significantly reduced (p < 0.05) and FSFI, HADS and SF-12 questionnaires revealed a significant improvement in sexual function, psychological wellbeing and quality of life (p < 0.05). The number of patients reporting the need for maintenance TCS treatment was reduced by 42% (p < 0.001) and an improvement in vulvar elasticity and color was reported in all patients. CONCLUSION: Following standard medical therapy, PRP may be effective not only in improving symptoms, but also in restoring function.

Histologic Subtypes in Endometriosis-Associated Ovarian Cancer and Ovarian Cancer Arising in Endometriosis: A Systematic Review and Meta-Analysis.

The definition of the association between ovarian cancer and endometriosis was first reported by Sampson in 1925. He identified the following criteria: (a) clear evidence of endometriosis in proximity to the tumour, (b) exclusion of a metastatic tumour to the ovary, (c) presence of tissue resembling endometrial stroma surrounding epithelial glands. The naming of these cancers is "endometriosis-associated ovarian cancer" (EAOC). Scott proposed an additional stringent criterion: evidence of histological transition from endometriosis to cancer is to define "ovarian cancer arising in endometriosis" (OCAE). The aim of this systematic review is to analyse the distribution of different ovarian cancer histotypes in EAOC and OCAE to understand their similarities and differences. A total of 31 studies were included. Four studies added data for both EAOC and OCAE. Twenty-three studies were selected for EAOC, with a total of 800 patients, and 12 studies were selected for OCAE, with a total of 375 patients. The results show no significant differences in the distribution of histotypes in the two populations analysed. Clear cell carcinoma (CCC) and endometrioid carcinoma (EC) were the most common subtypes and were less frequent in EAOC compared to OCAE; the odd ratios were 0.58 (0.26-1.29) and 0.65 (0.33-1.26) respectively, although the difference was not statistically significant. The other histotypes were present in small proportions. This analysis shows that the histological profiles of EAOC and OCAE are similar, suggesting a similar aetiopathological mechanism, which requires further research to investigate whether EAOC and OCAE may be in the same way but at different points of the process to malignancy or have different pathways of progression to malignancy.

Long-Term Follow-Up Outcomes in Women with In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix Undergoing Conservative Treatment-Cervical Adenocarcinoma Study Group Italian Society of Colposcopy and Cervico-Vaginal Pathology.

OBJECTIVE: The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. METHODS: Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan-Meier survival analysis with Logrank test were performed. RESULTS: Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47-26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). CONCLUSION: HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings.

"SO FAR AWAY" How Doctors Can Contribute to Making Endometriosis Hell on Earth. A Call for Humanistic Medicine and Empathetic Practice for Genuine Person-Centered Care. A Narrative Review.

"SO FAR AWAY" * How Doctors Can Contribute to Making Endometriosis Hell on Earth [* by Knopfler M. In Dire Straits. Brothers in Arms. Vertigo Records, U.K., 1985]. Abstract: The distance physicians may create within the relationship with their patients by not having a humanistic approach to their practice may strongly influence clinical outcomes. The purpose of this paper is to convey the well-known narrative of patient dissatisfaction into pro-action by discussing the aspects of dehumanization, which may occur in the relationship between physicians and women with endometriosis. Eight dimensions of dehumanization are examined and related to everyday scenarios occurring in endometriosis care settings and the possible downstream consequences on patients' clinical outcomes are described. Objectification, which may come across as minimization of pain, may not only increase patients' perception of pain but also lead to undertreatment of unrecognized forms of endometriosis, especially among adolescents. Passivity, that is not favoring shared decision-making nor self-management, may compromise adherence to treatment, reducing patients' trust in physicians and quality of life. The same consequences may result from homogenization, that is giving for granted that all patients have the same access to care. Both isolation, ie not practicing therapeutic empathy, and loss of meaning, ie not supporting patients in the re-definition of their life plans, may affect women's psychological wellbeing and further increase pain perception. Ignoring women's personal journey by not providing clear information on the consequences endometriosis may have on their lives may favor women's self-silencing. Not promoting an un-biased communication and not setting aside scientific polarization are the main features of dislocation, which may jeopardize patient empowerment. Lastly, having a reductionist approach to the body may contribute to chronicization of pain, thus compromising quality of life. This considered, taking time to listen to women with endometriosis and tailoring decisions on the basis of their individual needs should be fostered as a moral duty. Physicians should always keep in mind that they are not only deliverers of treatment; they are a form of treatment themselves.

Towards comprehensive management of symptomatic endometriosis: beyond the dichotomy of medical versus surgical treatment.

Except when surgery is the only option because of organ damage, the presence of suspicious lesions, or the desire to conceive, women with endometriosis-associated pain often face a choice between medical and surgical treatment. In theory, the description of the potential benefits and potential harms of the two alternatives should be standardized, unbiased, and based on strong evidence, enabling the patient to make an informed decision. However, doctor's opinion, intellectual competing interests, local availability of specific services and (mis)information obtained from social media, and online support groups can influence the type of advice given and affect patients' choices. This is compounded by the paucity of robust data from randomized controlled trials, and the anxiety of distressed women who are eager to do anything to alleviate their disabling symptoms. Vulnerable patients are more likely to accept the suggestions of their healthcare provider, which can lead to unbalanced and physician-centred decisions, whether in favour of either medical or surgical treatment. In general, treatments should be symptom-orientated rather than lesion-orientated. Medical and surgical modalities appear to be similarly effective in reducing pain symptoms, with medications generally more successful for severe dysmenorrhoea and surgery more successful for severe deep dyspareunia caused by fibrotic lesions infiltrating the posterior compartment. Oestrogen-progestogen combinations and progestogen monotherapies are generally safe and well tolerated, provided there are no major contraindications. About three-quarters of patients with superficial peritoneal and ovarian endometriosis and two-thirds of those with infiltrating fibrotic lesions are ultimately satisfied with their medical treatment although the remainder may experience side effects, which may result in non-compliance. Surgery for superficial and ovarian endometriosis is usually safe. When fibrotic infiltrating lesions are present, morbidity varies greatly depending on the skill of the individual surgeon, the need for advanced procedures, such as bowel resection and ureteral reimplantation, and the availability of expert colorectal surgeons and urologists working together in a multidisciplinary approach. The generalizability of published results is adequate for medical treatment but very limited for surgery. Moreover, on the one hand, hormonal drugs induce disease remission but do not cure endometriosis, and symptom relapse is expected when the drugs are discontinued; on the other hand, the same drugs should be used after lesion excision, which also does not cure endometriosis, to prevent an overall cumulative symptom and lesion recurrence rate of 10% per postoperative year. Therefore, the real choice may not be between medical treatment and surgery, but between medical treatment alone and surgery plus postoperative medical treatment. The experience of pain in women with endometriosis is a complex phenomenon that is not exclusively based on nociception, although the role of peripheral and central sensitization is not fully understood. In addition, trauma, and especially sexual trauma, and pelvic floor disorders can cause or contribute to symptoms in many individuals with chronic pelvic pain, and healthcare providers should never take for granted that diagnosed or suspected endometriosis is always the real, or the sole, origin of the referred complaints. Alternative treatment modalities are available that can help address most of the additional causes contributing to symptoms. Pain management in women with endometriosis may be more than a choice between medical and surgical treatment and may require comprehensive care by a multidisciplinary team including psychologists, sexologists, physiotherapists, dieticians, and pain therapists. An often missing factor in successful treatment is empathy on the part of healthcare providers. Being heard and understood, receiving simple and clear explanations and honest communication about uncertainties, being invited to share medical decisions after receiving detailed and impartial information, and being reassured that a team member will be available should a major problem arise, can greatly increase trust in doctors and transform a lonely and frustrating experience into a guided and supported journey, during which coping with this chronic disease is gradually learned and eventually accepted. Within this broader scenario, patient-centred medicine is the priority, and whether or when to resort to surgery or choose the medical option remains the prerogative of each individual woman.

Developing a set of patient-centered outcomes for routine use in endometriosis: An international Delphi study.

INTRODUCTION: There is large variation in individual patient care for endometriosis. A uniform approach to measure outcomes could be incorporated into routine clinical practice to personalize and monitor treatments and potentially improve the quality of care. The aim of this study is to identify a group of patient-centered outcomes for use in routine endometriosis care which are relevant to all patient profiles. MATERIAL AND METHODS: By means of a modified two-round Delphi study with international representation including healthcare professionals, researchers and patient representatives (51 participants, 16 countries) we developed a set of patient-centered measurements. The participants evaluated 47 Patient Reported Outcome Measures (PROMs) and 30 Clinician Reported Outcome Measures (CROMs) regarding their feasibility and relevance for their use in routine endometriosis care. After the two rounds of quotation, meetings of the experts were convened to participate in a final discussion to finalize the consensus of the final set of included measures. RESULTS: The final set of patient-centered outcomes includes six PROMs (measuring symptomatic impact, pain, work productivity and quality of life) and 10 CROMs (measuring clinical, imaging and surgical indicators). A supplementary list of outcomes was added to include important dimensions that were considered essential by the expert panel but are not relevant to all patients. In addition the need for development of specific tools (PROMs) measuring the psychological impact and the impact in sexual activity of endometriosis was highlighted. CONCLUSIONS: We have developed a set of patient-centered outcomes measures in endometriosis care. The selected outcomes comprise the common features for all patients suffering from endometriosis. adapted for use in routine practice. The list of outcomes has been adapted for use in routine practice from which clinicians can chose, depending on their needs.

Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adenomyosis. Part II: medical interventions.

According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen-progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed.

Proposal for targeted, neo-evolutionary-oriented, secondary prevention of early-onset endometriosis and adenomyosis. Part I: pathogenic aspects.

The potential for repeated ovulation and menstruation is thought to have provided a Darwinian advantage during the Palaeolithic. Reproductive conditions remained relatively stable until the pre-industrial era, characterized by late menarche, very young age at first birth, multiple pregnancies, and prolonged periods of lactational amenorrhoea. For hundreds of thousands of years, menstruators experienced few ovulatory cycles, even though they were genetically adapted to ovulate and menstruate every month. In the post-industrial era, the age at menarche gradually declined, the age at first birth progressively increased, and breastfeeding became optional and often of short duration. This created a mismatch between genetic adaptation and socio-environmental evolution, so that what was initially a probable reproductive advantage subsequently contributed to increased susceptibility to diseases associated with lifetime oestrogen exposure, such as ovarian, endometrial and breast cancer and, hypothetically, also those associated with the number of ovulatory menstruations, such as endometriosis and adenomyosis. The incidence of endometriosis shows a steep and progressive increase around the age of 25 years, but given the consistently reported delay in diagnosis, the actual incidence curve should be shifted to the left, supporting the possibility that the disease has its roots in adolescence. This raises the question of whether, from an evolutionary point of view, anovulation and amenorrhoea should not still be considered the physiological state, especially in the postmenarchal period. However, an increase in the frequency of endometriosis in recent decades has not been demonstrated, although this deserves further epidemiological investigation. In addition, as endometriosis occurs in a minority of individuals exposed to retrograde menstruation, other important pathogenic factors should be scrutinised. Research should be resumed to explore in more detail the transtubal reflux of not only blood, but also endometrial cells, and whether they are systematically present in the peritoneal fluid after menstruation. If repetitive ovulatory menstruation during the early reproductive years is shown to increase the risk of endometriosis and adenomyosis development and progression in susceptible individuals, hormonal interventions could be used as secondary prevention in symptomatic adolescents.

"The sound of silence" Giving voice to endometriosis-related positional dyspareunia.

Deep dyspareunia is one of the main symptoms of endometriosis. It appears to be submerged by a two-way disconnection between patients and their physicians. The aim of our review is to provide clear, ready-to-use advice on how to manage deep dyspareunia overcoming the gap in communication. Sexual history should always be taken as part of routine health care in these regards, using a patient-centered approach. An educational pelvic examination, which actively includes patients in the identification of painful areas, may prove useful to improve patients' understanding of their condition. Correlating painful pelvic areas with sexual positions and inviting patients to adopt alternative positions may represent a simple but extremely effective coping strategy to mitigate pain. Revealing and explaining to partners the nature of the pain is essential to allow them to take part in shared research of coping mechanisms, empowering the couple to make choices and changes. Couples who do not feel comfortable talking about intimacy by themselves may find that including a psychotherapist or a sexual therapist, may be a good way to start communication. Investigating and managing dyspareunia during medical encounters is a medical and ethical duty all healthcare practitioners should pursue.

Questionnaires for the Assessment of Central Sensitization in Endometriosis: What Is the Available Evidence? A Systematic Review with a Narrative Synthesis.

It has been suggested that central sensitization (CS) may be involved in the failure of standard medical and surgical treatment to relieve endometriosis-related pain. However, there is no gold standard for the diagnosis of CS, and self-reported questionnaires are used as diagnostic surrogates. The main objective of this review was to identify all CS questionnaires used in clinical endometriosis studies. The secondary objective was to qualitatively analyze strengths and weaknesses of each questionnaire. A PubMed and EMBASE systematic literature search conducted in April 2023 using the terms "endometriosis; central pain; central sensitization; questionnaire; patient-reported outcome measure; screening tool" identified 122 publications: six articles were included in the review. The Central Sensitization Inventory (CSI) is the most frequently used questionnaire for the detection of CS in patients with endometriosis. It has been validated in patients with endometriosis, in whom it appears to have good psychometric proprieties. The Fibromyalgia Survey Questionnaire (FSQ) has also been used, although it has not been specifically validated in endometriosis patients. The debate regarding these questionnaires' construct validity is still open and will be so until a gold standard diagnostic tool for CS is found. In fact, some authors argue these questionnaires are measuring psychological vulnerability and a hypervigilant state that is associated with pain, rather than CS itself. However, their use should not be discouraged as they are able to identify chronic pain patients which warrant further attention and who may benefit from broader treatment strategies.

Central Sensitization in Vulvodynia and Endometriosis: What Have We Been Overlooking So Far?

Importance: Women experience more frequent and greater pain than men, although they receive less adequate treatment and are perceived as more anxious than males. Recent clinical research has lead to hypothesize a common etiology for overlapping chronic pain conditions and mood disorders, namely, central sensitization, which originates from an alteration of pain processing pathways in the central nervous system. Objective: The aim of this review was to collect all available evidence regarding the potential role of central sensitization in vulvodynia and endometriosis. Evidence Acquisition: A systematic literature search was performed between July and August 2022 using the electronic database PubMed. The extracted data were summarized using a narrative approach. Results: Ten articles were chosen for the review. Participants' mean age was 39.2 years (SD = 5.1). Among serum markers of central sensitization, nitric oxide levels were greater in women with endometriosis than in controls, whereas brain-derived neurotrophic factor and S100B levels differed among pain conditions with structural anomalies and those without. Functional magnetic resonance imaging showed different resting state networks between patients with endometriosis and controls. In neurophysiology studies, cases had reduced pain thresholds, compared with healthy controls. Lastly, self-reported questionnaires suggested a central component of pain in women with endometriosis-related dyspareunia and associated bladder/pelvic floor tenderness. Conclusions and Relevance: The management of vulvodynia and endometriosis may benefit from a new perspective, which considers their possible central etiology. It is compelling that treatment of pain starts to be considered a therapeutic goal in its own right.

HPV-related lesions after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer: A focus on the potential role of vaccination.

OBJECTIVE: To date, no data supports the execution of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia (CIN2+) and early-stage cervical cancer. We aim to evaluate the potential effect of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer. METHODS: This is a multi-center retrospective study evaluating data of women who develop lower genital tract dysplasia (including anal, vulvar and vaginal intra-epithelial neoplasia) after having hysterectomy for CIN2+ and FIGO stage IA1- IB1 cervical cancer. RESULTS: Overall, charts for 77 patients who developed lower genital tract dysplasia were collected. The study population included 62 (80.5%) and 15 (19.5%) patients with CIN2+ and early-stage cervical cancer, respectively. The median (range) time between hysterectomy and diagnosis of develop lower genital tract dysplasia was 38 (range, 14-62) months. HPV types covered by the nonavalent HPV vaccination would potentially cover 94.8% of the development of lower genital tract dysplasia. Restricting the analysis to the 18 patients with available HPV data at the time of hysterectomy, the beneficial effect of nonvalent vaccination was 89%. However, considering that patients with persistent HPV types (with the same HPV types at the time of hysterectomy and who developed lower genital tract dysplasia) would not benefit from vaccination, we estimated the potential protective effect of vaccination to be 67% (12 out of 18 patients; four patients had a persistent infection for the same HPV type(s)). CONCLUSIONS: Our retrospective analysis supported the adoption of HPV vaccination in patients having treatment for HPV-related disease. Even in the absence of the uterine cervix, HPV vaccination would protect against develop lower genital tract dysplasia. Further prospective studies have to confirm our preliminary research.

Endometriosis and IVF treatment outcomes: unpacking the process.

Advanced endometriosis is associated with a reduction of IVF success. Surgical damage to the ovarian reserve following the excision of endometriomas has been claimed as a critical factor in the explanation of this detrimental effect. However, it is generally inferred that other mechanisms might also hamper IVF success in affected women. They include diminished responsiveness to ovarian stimulation, altered steroidogenesis, a decline in oocyte quality, reduced fertilization and embryo development, and impaired implantation. To navigate these limitations, we scrutinized available literature for studies specifically designed to address distinct phases of the IVF process. Utmost consideration was given to intra-patient ovarian response comparisons in women with unilateral endometriomas and to studies applying a meticulous matching to control confounders. The following observations have been drawn: 1) endometriosis has a negligible impact on ovarian response. A slight reduction in stimulation response can only be observed for endometriomas larger than 4 cm. Follicular steroidogenesis is unaffected; 2) oocyte quality is not hampered. Fertilization rates are similar, and intracytoplasmic sperm injection (ICSI) is not justified. Embryonic development is uncompromised, with no increase in aneuploidy rate; 3) endometrial receptivity is either unaffected or only slightly impacted. In conclusion, our study suggests that, aside from the well-known negative effect on ovarian reserve from excisional endometrioma surgeries, endometriosis does not significantly affect IVF outcomes.

Is endometrial receptivity affected in women with endometriosis? Results from a matched pair case-control study of assisted reproductive technology treatments.

RESEARCH QUESTION: Is endometriosis detrimental to embryo implantation? DESIGN: A retrospective matched case-control study of women with a surgical or ultrasound diagnosis of endometriosis at Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano between 2015 and 2021. Women with endometriosis who underwent a 'freeze-all' cycle during an IVF treatment were eligible to be included. They were matched to patients without the disease, who also underwent cryopreserved blastocyst transfer cycles, in a 1:1 ratio by age (±1 year), and number (=) and quality (±1 top versus low) of cryopreserved blastocysts. All women underwent single frozen embryo transfer, and assisted reproductive technology outcomes suggested by the Core Outcome Measure for Infertility Trials initiative were evaluated. The main outcome was the cumulative live birth rate per cycle. RESULTS: One hundred and one women with endometriosis and 101 matched unaffected women were included. Cumulative live birth rate per cycle did not vary between women with and without endometriosis (50% versus 58%, respectively; P = 0.32). On the basis of the Kaplan-Meier analysis, the predicted success rates over four embryos transferred were also similar (74% versus 82%, respectively; P = 0.67). CONCLUSION: In women with moderate or severe endometriosis, these retrospective results seem to indicate no or a limited effect of the disease on endometrial receptivity.