{"paper_id":"249b0d3d-771b-4644-9762-341cf8c5f471","body_text":"30\nReproductive Health  ●  August 2024  ●  Copyright © 2024 EMJ   ●   CC BY-NC 4.0 Licence\nEndometriosis, Endometrial Disorders, \nand Infertility: From Bench to Bedside\nSERUM PROGESTERONE LEVELS \nIN ENDOMETRIOSIS  \nThe session began with a presentation \nfrom Chloé Maignien, Cochin University \nHospital, France, reporting that serum \nprogesterone levels do not differ between \npatients with and without endometriosis \nwho conceived after hormone replacement \ntherapy-frozen embryo transfer (HRT-FET) \ncycles.1 It is well established that there is \na correlation between serum progesterone \nlevels around the time of HRT-FET and live \nbirth rate. Interestingly, when considering \nendometriosis, which frequently causes \ninfertility, progesterone resistance in the \nendometrium is common. Subsequently, it \nis hypothesised that these women require \nhigher progesterone levels to achieve a live \nbirth. Given the absence of evidence of this \nfrom controlled studies, Maignien’s research \nteam sought to compare progesterone levels \non the day of HRT-FET in patients with \nendometriosis/adenomyosis to controls  \nwho achieved a live birth. \nThe observational cohort study was \nconducted between January 2019–\nDecember 2021.1 Patients undergoing single \nautologous blastocyst FET using HRT with \nexogenous oestrogen and micronised \nvaginal progesterone were included. \nOestrogen treatment commenced on \nDay 1 of menstruation and continued for \napproximately 14 days, following which a \ntransvaginal ultrasound and blood testing \nwere performed. If endometrial thickness \nwas above 6 mm and progesterone level \nwas below 1.5 ng/mL, FET was scheduled, \nwith progesterone supplementation \ncommencing 5 days prior. Blastocysts \nwere transferred by senior gynaecologists \nand if the patient became pregnant, they \ncontinued the same luteal phase support \nuntil 12 weeks of gestation. \nIn total, 1,784 patients were included, \nwith 31.4% having endometriosis.1 Mean \nprogesterone levels on the day of FET was \n13.2 ng/mL (standard deviation: 4.8).1 The \noverall live birth rate was 31.4%, and 32% of \nthese patients who achieved a successful \nlive birth had a diagnosis of endometriosis.1 \nAmong women who conceived, there was \nno significant difference between the mean \nprogesterone levels on the day of FET when \ncomparing patients with endometriosis to \nthose without. Finally, considering patient \ncharacteristics and progesterone levels, \nAuthors: Abigail Craig, EMJ, London, UK\nCitation: EMJ Repro Health. 2024;10[1]:30-33.  \nhttps://doi.org/10.33590/emjreprohealth/GEAW7075.\nSPOTLIGHTING endometriosis, a session at the European Society of Human \nReproduction and Embryology (ESHRE) Annual Meeting, 2024, held in \nAmsterdam, the Netherlands, considered the latest advancements in the clinical \nmanagement of patients with this condition who are trying to conceive. Chaired by \nStacey Missmer, Michigan State University, East Lansing, USA, and Noortje van den \nBoogaard, Flevo Hospital, Almere, the Netherlands, six presentations were delivered \nto a packed auditorium.\nSerum progesterone levels do not differ \nbetween patients with and without \nendometriosis who conceived after \nhormone replacement therapy-frozen \nembryo transfer (HRT-FET) cycles\nCongress Feature  ●  ESHRE 2024\n\nCC BY-NC 4.0 Licence  ●  Copyright © 2024 EMJ   ●   August 2024  ●  Reproductive Health\n31\nneither the presence of endometriosis nor \nadenomyosis were related with a significant \ndifference. However, factors such as BMI, \nduration of infertility, and geographic origin \nsignificantly affected progesterone levels. \nThus, Maignien concluded that they found \nno difference between progesterone levels \nin patients with endometriosis and controls \non the day of FET, and therefore, patients \nwith endometriosis do not require higher \nprogesterone levels to achieve a pregnancy. \nSUBCUTANEOUS PROGESTERONE \nSUPPLEMENTATION IN FROZEN \nEMBRYO TRANSFER\nThe second talk, delivered by Noémie \nSachs-Guedj, Dexeus University Hospital, \nBarcelona, Spain, also considered \nserum progesterone in patients with \nendometriosis, but focused on artificial \ncycle FET (AC-FET).1 She began by \nhighlighting that several studies report  \non the best preparation protocol for patients \nwith endometriosis, noting that recent \nstudies suggest AC-FET is the  \nmost appropriate protocol, as it may  \nhelp prevent endometrial alterations by \ninducing ovarian suppression and reducing \ninflammation. Due to the absence of a \ncorpus luteum, preparing the endometrium \nis crucial in these patients. The standard \nprocedure for this is 2 mg oestrogen \ntaken three times per day. If an ultrasound \nindicates an endometrial thickness of \nover 7 mm, 200 mg of micronised vaginal \nprogesterone is delivered three times per \nday. Despite this, recent studies suggest \nserum progesterone levels of less than \n10 ng/mL are linked to poorer outcomes. \nTo combat this, Sachs-Guedj outlined \na new protocol that uses subcutaneous \nprogesterone supplementation of 25 mg/\nday if the serum progesterone level is  \nnot above 10.6 ng/mL the day prior to \nembryo transfer.2 Specifically considering \npatients with endometriosis, this protocol \nmay require adjustment as the condition  \ndisrupts the balance between  \nprogesterone and oestrogen. \nInvestigating this further, Sachs-Guedj and \nteam sought to consider progesterone levels \nin patients with endometriosis and whether \nsubcutaneous progesterone would aid  \nthose below the progesterone cutoff \nachieve similar live birth rates to those \nwithout endometriosis. A retrospective \ncohort study between January 2019–\nDecember 2022 suggested that mean \nprogesterone levels on the day of transfer \nwere comparable between patients with and \nwithout endometriosis.2\nAdditional analysis of the study data, \nusing a multivariable logistic regression \nincluding 985 AC-FET cycles, specifically \ninvestigated the effect of subcutaneous \nprogesterone supplementation. Patients \nwith endometriosis and progesterone levels \nbelow 10.6 ng/mL receiving subcutaneous \nsupplementation were the reference \ngroup. Results showed comparable live \nbirth rates between the reference group \nand all other test groups, with and without \nendometriosis, with progesterone levels \nabove or below 10.6 ng/mL, receiving or not \nreceiving supplementation. \nOverall, Sachs-Guedj concluded AC-FET \ncycles in patients with endometriosis \nrequiring subcutaneous progesterone \nachieve live birth rates comparable to both \nendometriosis and non-endometriosis \ncycles with the correct progesterone levels \nbefore FET. Thus, supplementation does \nnot need to be altered when delivered \nto patients with endometriosis and \nthe protocol allows cost-effective and \nconvenient luteal phase individualisation. \nDOES ENDOMETRIOSIS AFFECT \nOOCYTE MORPHOLOGY?  \nIpek Nur Balın Duzguner, Istanbul Memorial \nHospital, Türkiye, delivered the third \nresearch presentation of the session, \nfocusing on whether endometriosis affects \noocyte morphology.3 Previous conflicting \nevidence meant the research team aimed \nto investigate this relationship using a \nretrospective, single-centre study  \nbetween August 2011–March 2023. 3 \nESHRE 2024  ●  Congress Feature\n\n32\nReproductive Health  ●  August 2024  ●  Copyright © 2024 EMJ   ●   CC BY-NC 4.0 Licence\nOverall, 29,130 assisted reproductive \ntechnology cycles were included in the \nstudy.3 There were 4,602 cycles originating \nfrom patients with endometriosis and \n24,528 cycles from patients without \nendometriosis, permitting the study of \n27,204 oocytes and 178,774 oocytes, \nrespectively. 3 Various parameters, such as \npresence of vacuole(s) and zona pellucida \ndefects, were assessed individually to \nidentify abnormal oocyte morphology. \nFollowing statistical analysis, the number of \nprevious unsuccessful cycles, duration of \ninfertility, and anti-mullerian hormone levels \nwere significantly different between the \ntwo test groups. 3 The oocyte morphological \nabnormalities evaluated were cytoplasmic \ngranulation, large perivitelline space, zona \nabnormalities, and polar body defects.3 \nThese were significantly increased in \npatients with endometriosis. \nHowever, when considering the effect size, \nthere was no significant difference between \nthe two groups, due to the large number \nof oocytes. 3 Further analysis focused \non pregnancy results, specifically single \nblastocyst FET cycles (n=11,116).  3 Clinical \nand total pregnancy loss was significantly \nhigher in patients with endometriosis, but \nagain, the effect size suggested this result \nwas negligible. \nOverall, no significant differences were \nfound between the endometriosis and \nnon-endometriosis groups when oocyte \nmorphological abnormalities were evaluated \nusing effect size. \n29,130 \n4,602\n24,528\nassisted reproductive technology \ncycles were included in the study\ncycles originating from  \npatients with endometriosis\ncycles from patients  \nwithout endometriosis\nTHE ENDOMETRIOSIS \nLONGITUDINAL FERTILITY STUDY\nVanessa Ross, Royal Women’s Hospital, \nMelbourne, Australia, delivered the \nfourth talk, which outlined the outcomes \nand interim data of the Endometriosis \nLongitudinal Fertility Study (ELFS) \nstudy, specifically focusing on outcomes \nfor women with moderate or severe \nendometriosis trying to conceive.4 After \nreminding the audience that endometriosis \nis associated with reduced natural and \nassisted conception rates, she stressed that \nthere is still limited data available to advise \ntreatment recommendations, as studies \nare commonly retrospective cohort studies \nthatlack a control group. Whilst laparoscopic \nsurgery has been explored as a treatment \noption, due to the increased risks  \nassociated with surgical intervention \nrobust evidence is required regarding its \neffectiveness in improving fertility in patients \nwith endometriosis. \nTherefore, the research group aimed to \nexplore the role of surgery for infertility \nin patients with moderate or severe \nendometriosis, as well as the use of pre-\nemptive surgical treatment. The ELFS study, \nEndometriosis is associated  \nwith reduced natural and  \nassisted conception rates\nCongress Feature  ●  ESHRE 2024\n\nCC BY-NC 4.0 Licence  ●  Copyright © 2024 EMJ   ●   August 2024  ●  Reproductive Health\n33\na multi-site longitudinal cohort study, is \ncurrently recruiting women <38 years of \nage, and aims to assess clinical pregnancy \nand live birth rates in those with evidence of \nmoderate to severe endometriosis.4 \nFollowing enrolment, participants  \ncomplete a baseline questionnaire,  \nbefore downloading a smart phone app  \nthat delivers periodic cyclical  \nquestionnaires. Finally, pregnancy  \noutcome data is collected.4\nIn total, 868 completed cycles from 151 \nparticipants have been captured so far.  \nThe majority of participants (70%) elected \nto undergo surgical treatment during the \nstudy period. 4 Furthermore, 54 participants \nhave recorded that they are trying to \nconceive, with 193 attempted conception \ncycles recorded (53 of these through in \nvitro fertilisation). 4 In total, 33 pregnancies \nwere recorded, with a fecundity of 17%, \nwhich Ross noted was surprising due to \nthe low average age of the cohort.4 Seven \nmiscarriages and one termination were  \nalso recorded.4 \nRoss concluded by addressing the study \nlimitations. Namely, as it is not a prospective \nrandomised control trial, cofounders are  \nnot accounted for. Furthermore, in \nthe absence of robust data regarding \nmanagement, clinician scope and practice, \nand pain symptoms may influence \nrecommendations for patient management. \nCONCLUDING REMARKS \nIn conclusion, the session provided \nvaluable insights into the complexities \nof endometriosis, endometrial disorders, \nand infertility. Through a series of detailed \npresentations, researchers highlighted \nkey findings and advancements in the \nclinical management of these conditions. \nNotably, studies on serum progesterone \nlevels revealed no significant differences in \npatients with endometriosis, challenging the \nassumption that higher progesterone levels \nare necessary for successful conception. \nOverall, there was an emphasis on the need \nfor continued research and individualised \ntreatment approaches to improve fertility \noutcomes for women with endometriosis  \nand other endometrial disorders.\nReferences\n1. Bourdon M et al. Serum Progesterone \nlevels do not differ between patients \nwith endometriosis and unaffected \npatients who conceive after Hormone \nReplacement Therapy-Frozen Embryo \nTransfer (HRT-FET) cycles. Abstract \nO-146. ESHRE Annual Meeting, 7-10 \nJuly, 2024.  \n \n \n2. Sachs Guedji N et al. Role of serum \nprogesterone levels and subcutaneous \nprogesterone supplementation in \nendometriosis patients undergoing \nArtificial Cycle Frozen Embryo \nTransfer. Abstract O-147. ESHRE \nAnnual Meeting, 7-10 July, 2024. \n3. Duzguner INB et al. Does presence \nof endometriosis adversely affect \noocyte morphology? Evaluation of \na large number of oocytes obtained \nfrom endometriosis patients, 27204 \noocytes. Abstract O-148. ESHRE \nAnnual Meeting, 7-10 July, 2024. \n4. Ross V et al. The Endometriosis \nLongitudinal Fertility Study (ELFS): \nOutcomes for women with moderate \nor severe endometriosis who are trying \nto conceive. Abstract O-149. ESHRE \nAnnual Meeting, 7-10 July, 2024. \nESHRE 2024  ●  Congress Feature","source_license":"CC0","license_restricted":false}