Reproductive Outcome After Laparoscopic Ovarian Endometrioma Stripping With Volumetric Hydrodissection.

Study question Is there an association between the composition of the endometrial microbiota and the reproductive outcomes in infertile patients undergoing in vitro fertilization (IVF)? Summary answer The composition of the endometrial microbiota (EM) prior to embryo transfer is associated with the different reproductive outcomes: live birth, no pregnancy or clinical miscarriage. What is known already The investigation of bacterial communities in the female reproductive tract using molecular methods has revealed the existence of a continuum microbiota that extends from the vagina to the upper genital tract. Previous evidence suggests the existence of an association between the vaginal and endometrial microbiome composition with reproductive and obstetrical outcomes. Specifically, the presence of specific pathogens together with low abundance of Lactobacilli has been associated with poor IVF outcomes. Study design, size, duration Multicentre prospective observational clinical study analysing the EM of infertile patients undergoing IVF (with maternal age ≤40) or ovum donation (≤50 years). A total of 452 infertile patients undergoing IVF/ovum donation were assessed for eligibility in 13 reproductive clinics in Europe, America, and Asia. The duration of the study was 30 months and the recruitment period extended between August 2017 and February 2019 (ct.gov 03330444). Participants/materials, setting, methods Endometrial fluid and endometrial biopsy were collected during a hormonal replacement therapy cycle after 5 days of progesterone (P) administration prior to a frozen embryo transfer cycle. Endometrial microbiota (EM) composition was analyzed using 16S rRNA gene sequencing using compositional data to transform scale-invariant values in both sample types. The EM in fluid and biopsy was associated with live birth, biochemical pregnancy, clinical miscarriage, or no pregnancy. Main results and the role of chance Of the 452 patients assessed, 44 did not meet the selection criteria and were excluded for the study and 66 patients were lost to follow-up. Of the 342 remaining patients, 198 (57.9%) became pregnant [141 (41.2%) had a live birth, 27 (7.9%) had a biochemical pregnancy, 2 (0.6%) had an ectopic pregnancy, and 28 (8.2%) a clinical miscarriage], while 144 (42.1%) did not become pregnant. The baseline characteristics, clinical and embryological variables were homogeneous and no bias toward the clinical outcome categories was observed. Our association study showed that the composition of the EM was associated with the reproductive outcome in both endometrial fluid and biopsy. A dysbiotic endometrial microbiota profile composed of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus and Streptococcus was significantly associated with unsuccessful outcomes, especially no pregnancy and clinical miscarriage. In contrast, Lactobacillus was consistently enriched in patients with live birth outcomes. The EM in endometrial fluid did not fully reflect that in endometrial biopsy, although their association with clinical outcome was consistent. Limitations, reasons for caution The main limitation was the small number of biochemical pregnancy and clinical miscarriage analysed. During transcervical collection of endometrial samples caution was taken to avoid contamination with the cervix although cervical contamination cannot be fully discarded. Wider implications of the findings Our data indicate that EM dysbiosis is associated with poor clinical outcome in ART. Thus, the EM composition before embryo transfer could be a useful biomarker to consider offering an opportunity to further improve diagnosis and treatment strategies. Trial registration number Clinical trials.gov 03330444

Retained products of conception following delivery or early pregnancy failure are often treated by operative hysteroscopy. We aimed to evaluate reproductive and obstetric outcomes following operative hysteroscopy for treatment of retained products of conception. We also investigated the effect of time interval between operative hysteroscopy and pregnancy on these outcomes. A retrospective cohort study conducted at the gynecology department of a tertiary teaching hospital between January 2012 and December 2016. Included were women who underwent operative hysteroscopy for treatment of retained products of conception and became pregnant following the procedure. Reproductive and obstetric data were retrieved from electronic medical records and by telephone questionnaire. The effect of time interval between operative hysteroscopy and pregnancy on reproductive outcomes was also evaluated by comparing women who conceived 6 months or less and women who conceived more than 6 months following surgery. Seventy-nine women who underwent operative hysteroscopy for treatment of retained products of conception and who conceived later were included. Mean time from women's attempt to conceive to conception was 4.6 (SD=6.4) months. Conception rate was 84.8% at 6 months and reached 92.4% at 12 months postsurgery. Miscarriage rate for the consecutive pregnancy following hysteroscopy was 15.2% and delivery rate was 84.8%. Two cases of obstetric complications including one case of retained placenta and one case of post-partum hemorrhage were noted. Time interval between operative hysteroscopy and pregnancy did not affect reproductive or obstetric outcomes. Women treated by operative hysteroscopy for retained products of conception have no negative reproductive and obstetric outcomes. Time interval between the procedure and pregnancy has no effect on these outcomes.

STUDY QUESTION What is the long-term reproductive health outcome of patients who have undergone testicular sampling for fertility preservation (FP) before and during the pubertal transition period? SUMMARY ANSWER In long-term follow-up after testicular sampling for FP, hormonal data showed that 33% of patients had primary seminiferous tubule insufficiency (high FSH) while semen analyses showed 52% of patients having a severe reduction in total sperm counts or complete absence of ejaculated sperm. WHAT IS KNOWN ALREADY During childhood and adolescence, both treatments for cancer and benign haematological diseases that require a bone marrow transplantation, can be detrimental to spermatogenesis by depleting the spermatogonial stem cell population. A testicular biopsy prior to chemotherapy or radiotherapy, even though still an experimental procedure, is now recommended for FP by European and USA oncofertility societies if performed within an institutional research setting. While short-term follow-up studies showed little to no post-operative complications and a normal testicular development after 1 year, data regarding the long-term follow-up of boys who have undergone this procedure are still lacking. STUDY DESIGN, SIZE, DURATION This is a longitudinal retrospective cohort study that reports on the long-term follow-up of pre- and peri-pubertal boys who have undergone a testicular biopsy for FP between May 2005 and May 2020. All the patients included in this study were referred to our programme by haematologists-oncologists who are part of a regional multi-centric collaborative care pathway. PARTICIPANTS/MATERIALS, SETTING, METHODS Of the 151 boys referred to our FP programme, 139 parents/legal guardians accepted that their child undergo a testicular biopsy. Patient characteristics (i.e. age at biopsy, urogenital history, pubertal status at diagnosis), indications (disease type and dosage of gonadotoxic treatments), operative and post-operative data (biopsy volume, surgical complications), anatomopathological analyses (presence/absence of spermatogonia, Johnsen score) and reproductive data (semen analyses, FSH, LH, testosterone levels) were collected from the institutions’ FP database and medical records or from the ‘Brussels Health Network’. Cumulative alkylating agent treatment was quantified using the cyclophosphamide equivalent dose (CED). Patients who were 14 years or older at the time of the follow-up and in whom the testicular tissue was shown to contain spermatogonia were included in the reproductive outcome analysis. Comparison of the sperm count findings (absence/presence of spermatozoa) and FSH levels (high (≥10 IU/l)/normal) between patients who were either pre- (Tanner 1) or peri-pubertal (Tanner >1) at the time of the biopsy was done using the Mann–Whitney U or Fisher’s tests. A multiple logistic regression was used to study the relationship between the hormone reproductive outcome (high versus normal FSH), as a proxy marker for fertility, and both the pubertal status (Tanner 1 versus Tanner >1) and Johnsen score at the time of the biopsy, while adjusting for CED. MAIN RESULTS AND THE ROLE OF CHANCE A testicular biopsy was performed in 139 patients either before (129/139) or after (10/139) the start of a gonadotoxic treatment. Post-operative complications occurred in 2.1% (3/139). At the time of the procedure, 88% (122/139) of patients were pre-pubertal and 12% (17/139) were peri-pubertal. The presence of spermatogonia was documented in 92% (128/139) of cases. Follow-up data were available for 114 patients after excluding 23 deceased and two patients lost to follow-up. A paediatric endocrinologist’s follow-up including clinical examination and data on reproductive hormones was available for 57 patients (age ≥14) and 19 (33%) of these were found to have high FSH levels (20 ± 8.8 IU/l). There were 37 patients who had returned to the reproductive specialist’s consultation for post-treatment fertility counselling and results on semen analysis were available in 27 of these cases; 14/27 (52%) had severely impaired semen parameters including 8 who were azoospermic. Among patients who received an alkylating agent-based treatment (n = 42), a peri-pubertal status (Tanner >1) at the time of diagnosis/biopsy was found to be associated with a higher risk of having primary testicular failure (defined by an FSH ≥ 10 IU/l) after treatment completion with an OR of 6.4 (95% CI 1.22–33.9; P = 0.03). Of all the patients, 2.6% had already fulfilled their wish to build a family or were actively seeking parenthood. LIMITATIONS, REASONS FOR CAUTION Although this is the largest cohort with follow-up data providing proxy markers of the reproductive potential of boys in whom a testicular biopsy for FP was performed before puberty or during the pubertal transition period, the amount of data provided is limited, and originating from a single programme. Further data collection to confirm the observations in other settings is therefore awaited. WIDER IMPLICATIONS OF THE FINDINGS Testicular sampling for FP should be offered to boys at risk of losing their fertility (and is recommended for those at high risk) as part of ethically approved research programmes. Long-term follow-up data on increasing numbers of boys who have undergone an FP procedure will help improve patient care in the future as patient-specific factors (e.g. urogenital history, age at gonadotoxic therapy) appear to influence their reproductive potential after gonadotoxic therapies. STUDY FUNDING/COMPETING INTEREST(S) FNRS-Télévie, the Salus Sanguinis Foundation and the Belgian Foundation against Cancer supported the studies required to launch the FP programme. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

BackgroundBreast cancer is the most common cancer in young women. Fortunately current survival rates of BC are significant which makes future fertility very important for quality of life of BC survivors. Chemotherapy carries a significant risk of infertility in BC patients so it is important to support fertility preservation decisions in premenopausal women. Amenorrhea has long been used as a surrogate marker of infertility in cancer patients but more reliable ovarian reserve (OR) markers are available. This study aimed to prospectively measure levels of OR in a cohort of young women with breast cancer exposed to chemotherapy, to identify adverse reproductive health outcomes in this population and to assess the influence of patient and treatment-related factors in those outcomes.MethodsThis prospective observational study included premenopausal women with breast cancer aged 18–40 years at diagnosis and proposed for (neo) adjuvant chemotherapy. Patients were evaluated before, during and a minimum of 9 months after the end of chemotherapy. Reproductive health outcomes: menses, hormonal and ultrasound OR markers, recovery of ovarian function and Premature Ovarian Insufficiency (POI).ResultsA total of 38 patients were included (mean age 32.9 ± 3.5 years). Levels of OR significantly decreased during the study. At the last follow up, 35 patients had AMH below the expected values for age; eight presented postmenopausal FSH; ten had not recovered their ovarian function and five met the defined criteria for POI. Age and baseline AMH were positively correlated with AMH at the last follow-up. AMH levels were higher in the group of patients treated with trastuzumab and lower in those under hormonal therapy, at the last follow-up.ConclusionsSignificant effects of systemic treatments on several reproductive outcomes and a strong relation of those outcomes with patient’s age and baseline level of AMH were observed. Our results point to a possible lower gonadotoxicity when treatment includes targeted therapy with trastuzumab. Also, this investigation highlights the lack of reliable OR markers in women under hormonal therapy.

Vaporization of ovarian endometrioma using plasma energy: histologic findings of a pilot study

Study question What are the long-term outcomes after fertility preservation (FP) with versus without controlled ovarian stimulation (COS) in women with BC? Summary answer FP with COS was associated with higher rates of post-BC ART-treatment, while the rates of livebirth and all-cause mortality were similar between the two FP-groups. What is known already BC is the most common cancer in women of reproductive age, and the most common indication for female FP in Sweden. FP-methods including cryopreservation of oocytes, embryos and ovarian tissue are offered at Swedish academic centers within the health insurance coverage available to all citizens. A COS treatment is usually completed in 2-3 weeks, while ovarian tissue cryopreservation does not need COS and can be performed within a few days. To date, data on long term reproductive and oncologic outcome in women with BC undergoing FP with vs without COS are scarce. Study design, size, duration Multicenter nationwide cohort study aiming to investigate differences in long-term outcomes of women with BC receiving FP with or without COS at one of the seven regional FP programs in Sweden during 1994 - 2017 (N = 425). Participants/materials, setting, methods During the study period, 367 women received FP with COS (exposed) and 58 women underwent cryopreservation of ovarian tissue (unexposed) at Swedish centers. Reproductive outcomes, including post-diagnosis livebirths and the use of ART, as well as all-cause survival were investigated by linking of individuals in the cohort to several Swedish population-based registers. Outcomes among the women exposed and unexposed to COS were compared using Cox proportional hazard models adjusted for sociodemographic-, disease- and treatment characteristics. Main results and the role of chance Of 367 women exposed to FP with COS, 80 (22%) had at least one post-diagnosis livebirth (mean follow-up 4.3 years), compared to 17 (29%) of 58 women who underwent ovarian tissue cryopreservation (mean follow-up 5.9 years). Rates of ART-use during the follow-up were significantly higher in the group with COS (adjusted hazard ratio, aHR: 3.3, 95% CI:1.0-10.8), while livebirth rates (aHR: 1.1, 95% CI:0.6-2.0) as well as all-cause mortality rates (aHR:1.1, 95% CI:0.4-2.7) were similar between the groups. The five-years and ten-years cumulative incidence of post-BC livebirths was 18.3% and 41.4% among exposed to COS versus 23.7% and 38.9% among women with cryopreservation of ovarian tissue. Limitations, reasons for caution The FP programs in Sweden may differ from those in other countries, however data from population-based registers usually provide diversity. In Sweden, the use of gestational carriers is not permitted, thus individuals in this cohort had to achieve and carry by themselves the pregnancies resulting in post-BC livebirths. Wider implications of the findings The study results provide reassuring real-world reproductive and oncologic data following FP, both with and without COS, in women with BC. Our analyses are adjusted for identified confounders, and provide valuable information for FP-counselling of women with BC in need of FP. Trial registration number not applicable

Anti-Müllerian hormone (AMH) and antral follicular count (AFC) decrease in women with ovarian endometrioma (OMA) and in vitro fertilization (IVF). In addition, these parameters drop even further when women with OMA undergo surgery. In this study, the primary aim was to compare the reproductive variables in IVF-treated women with and without endometriosis. The secondary aim was to explore if the reproductive variables were modified by endometrioma surgery. In this retrospective study, 244 women undergoing IVF were enrolled at the Hospital Universitario La Paz (Madrid, Spain). Women were categorized as OMA not surgically treated (OMA; n = 124), OMA with surgery (OMA + S; n = 55), and women with infertility issues not related to OMA (control; n = 65). Demographic and clinical variables, including age, body mass index (BMI), and reproductive (AMH, AFC, number of extracted oocytes, and transferred embryos) and obstetrical data (biochemical pregnancy and fetal heart rate at 6 weeks) were collected. Adjusted logistic regression models were built to evaluate reproductive and pregnancy outcomes. The models showed that women with OMA (with and without surgery) had significantly decreased levels of AMH and AFC and numbers of cycles and C + D embryos. Women with OMA + S had similar rates of pregnancy to women in the control group. However, women with OMA had lower biochemical pregnancy than controls (aOR = 0.08 [0.01; 0.50]; p-value = 0.025). OMA surgery seems to improve pregnancy outcomes, at least until 6 weeks of gestation. However, it is important to counsel the patients about surgery expectations due to the fact that endometrioma itself reduces the quality of oocytes.

There is limited evidence on the impact of bariatric surgery (BS) on reproductive outcomes in the general population and specifically in patients with polycystic ovarian syndrome (PCOS) or the effect of different BS techniques. The study aims to investigate the impact of BS on fertility, pregnancy, and newborn outcomes in reproductive age women who have undergone BS and the outcomes according to surgical procedure and PCOS diagnosis. This was a retrospective, descriptive, cross-sectional study performed in women from 18-39 years undergoing BS in our centre from January 2005 to December 2010. We performed a telephone interview including a structured reproductive health survey on fertility, pregnancy, and offspring outcomes before and after BS. Of the women, 872 underwent BS during the study period, 298 were 18-39 years old, and reproductive data was obtained from 217. Women with regular menstrual cycles increased from 52.9% before BS to 72.9% 1 year after surgery. The percentage of patients with a time-to-pregnancy longer than 12 months was higher after laparoscopic sleeve gastrectomy (LSG) (17.8%) compared to laparoscopic Roux-en-Y gastric bypass (7.1%; p = 0.02). Menstrual regularity was less frequent in PCOS (n = 43) (26.0%) compared to non-PCOS women before BS (60.1%; p = 0.01), with no differences after surgery. Several perinatal results showed an improvement after BS, with a reduction in macrosomia rate and birth weight. BS was associated with an improvement in several reproductive outcomes. Menstrual regularity was especially improved in PCOS women. Further research may clarify the impact of LSG on fertility.

Study question What is the association of BMI(Body-Mass-Index) with serum and follicular fluid leptin levels and their effect on reproductive outcomes? Summary answer Increasing-BMI has direct correlation with-leptin-levels. However, increasing leptin-levels did-not alter reproductive-outcomes. Use of leptin as biomarker in women of high-BMI to predict-reproductive-outcomes needs further evaluation. What is known already Obesity in women alters reproductive outcomes through menstrual and ovulatory disorders, impaired endometrial development and decreased embryo implantation. Numerous studies investigating the impact of elevated BMI on reproductive outcomes have shown conflicting results. Leptin is a 16-kDa protein hormone released from white adipose tissue. It regulates appetite and body weight. Therefore women with obesity have shown to have higher levels of Leptin. Leptin has been thought to exert its effects on reproduction via-HPO-axis-(Hypothalamo-Pituitary-Ovarian),but there might also be a direct ovarian effect. Literature suggests that high serum and/or follicular fluid leptin concentrations have correlated negatively with IVF(in-Vitro Fertilization) cycle outcomes Study design, size, duration A Prospective-Observational-Cohort-study conducted over a duration of 8months from May2023-December2023 at our center with prior approval from Institutional-Ethical-Committee(IEC)( IEC No: RECR/1312/Inst/TG/2019/021). The sample size of 98 women for this study, which was derived by assuming 80% power of the study and significance level at 5%. Women were divided into groups based on BMI and Leptin levels. Only self-gamete-cycles with female-age in-between 21-37yrs were considered for this study. Cycles with genetic-testing on embryos(PGT) were excluded. Participants/materials, setting, methods All participants underwent controlled-ovarian-stimulation as per-SOP. On the day of oocyte retrieval, their serum/follicular-fluid samples were collected and Leptin-levels were quantified using-Abkine-Leptin-ELISA-kit(Manufacturer’s protocol followed). Normal-Leptin-level-0.5-15.2 ng/ml Higher-Leptin-level->15.2 ng/ml All participants underwent Frozen Embryo Transfers(FET) with 1or2 vitrified-Warmed good-grade-Blastocysts that showed 100%survival. Participants were divided into the following-BMI-groups Normal BMI(n = 43)-18-24.9 Over-weight BMI(n = 33)-25-29.9 Obese BMI(n = 22) >30 Outcome of their FET was recorded based on BMI and Leptin-levels.. Data was statistically analyzed using SAS software. Main results and the role of chance Effect of BMI on outcomes: Mean duration-of-stimulation across various BMI groups was comparable Mean-dosage-of-Gonadotrophins was higher in BMI>30(pvalue-0.002- Significant)) Mean-oocytes-collected, maturity-rates, Fertilization-rates and Blastocyst-formation-rates were comparable across all BMI-groups. As BMI increased the pregnancy-outcomes decreased as shown below: Normal BMI Vs Overweight Vs Obese BMI-respectively Miscarriage Rate(MR)-0%(Vs)6.6%(Vs)17%(p = 0.001-Significant) IR-63%(Vs)35%(Vs)9%(p = 0.001-Significant) LBR-62.1%(Vs)42.4%(Vs)13.6%(p = 0.006- Significant) As per the data, BMI seems to have a negative-correlation with reproductive-outcomes. Mean levels of Leptin(serum/follicular fluid across BMI groups, Normal BMI Vs Overweight Vs Obese BMI respectively are described below: 14ng/ml(Vs)17.9ng/ml(Vs)19.6 ng/ml(p = 0.001- Significant) As the BMI increases, the serum/follicular-fluid-Leptin-levels also increase and the levels were similar and comparable in both the body-fluid samples(follicular & Serum). Data from this study suggests that serum Leptin levels can be a surrogate marker for Follicular-Leptin-levels Association of Leptin levels and Reproductive outcomes: Normal Leptin levels(Vs)Raised-Leptin respectively shown below: IR-42%(Vs)38%(p = 0.68-NS) MR-14.3%(Vs)12.1%(p = 0.20-NS) LBR-46.2%(Vs)40.3%(p = 0.76-NS) There seemed a poor correlation/association of Leptin levels and reproductive outcomes. The outcomes were comparable between normal and raised-Leptin-levels. Though data from this study infers that there is a direct correlation between BMI and Leptin-levels, there seemed no correlation between Leptin-levels and reproductive-outcomes. Utilising serum/follicular leptin-levels as a biomarker in obese-women to predict-reproductive-outcomes does not seem to help. Limitations, reasons for caution Larger sample size is required to make statistically significant conclusions regarding effect of serum leptin level on IVF success. Other causes of implantation failure like genetic abnormality in embryo, displaced window of implantation etc were not ruled out. Wider implications of the findings Further research needs to be done on the effectiveness of serum leptin level measurement as a predictor of IVF success in obese individuals. Trial registration number No

This review discusses current diagnostic techniques for müllerian anomalies, reproductive outcome data, and management options in reproductive-age women. Multiple retrospective studies have investigated reproductive outcomes with müllerian anomalies, but few current prospective studies exist. Uterine anomalies are associated with normal and adverse reproductive outcomes such as recurrent pregnancy loss and preterm delivery, but not infertility. Furthermore, unicornuate, didelphic, bicornuate, septate, arcuate, and diethylstilbestrol-exposed uteri have their own reproductive implications and associated abnormalities. Common presentations of müllerian anomalies and current diagnostic techniques are reviewed. Surgical intervention for müllerian anomalies is indicated in women with pelvic pain, endometriosis, obstructive anomalies, recurrent pregnancy loss, and preterm delivery. Although surgery for most uterine anomalies is a major intervention, the uterine septum is preferentially managed with a hysteroscopic procedure. Several recent studies and review articles discuss management of the septate uterus in asymptomatic women, infertile women, and women with a history of poor reproductive outcomes. Current assessment of reproductive outcomes with uterine anomalies and management techniques is warranted. Müllerian anomalies, especially uterine anomalies, are associated with both normal and adverse reproductive outcomes, and management in infertile women remains controversial.

Impact of adenomyosis on IVF outcomes in women undergoing donor oocyte transfers: a prospective observational study

To determine the relationship between affective measures and cognition before and after non-cardiac surgery in older adults. Observational prospective cohort study in 103 surgical patients age ≥ 60 years old. All participants underwent cognitive testing, Center for Epidemiologic Studies-Depression, and State Anxiety Inventory screening before and 6 weeks after surgery. Cognitive test scores were combined by factor analysis into 4 cognitive domains, whose mean was defined as the continuous cognitive index (CCI). Postoperative global cognitive change was defined by CCI change from before to after surgery, with negative CCI change indicating worsened postoperative global cognition and vice versa. Lower global cognition before surgery was associated with greater baseline depression severity (Spearman's r = -0.30, p = 0.002) and baseline anxiety severity (Spearman's r = -0.25, p = 0.010), and these associations were similar following surgery (r = -0.36, p < 0.001; r = -0.26, p = 0.008, respectively). Neither baseline depression or anxiety severity, nor postoperative changes in depression or anxiety severity, were associated with pre- to postoperative global cognitive change. Greater depression and anxiety severity were each associated with poorer cognitive performance both before and after surgery in older adults. Yet, neither baseline depression or anxiety symptoms, nor postoperative change in these symptoms, were associated with postoperative cognitive change.

Reproductive and Obstetric Outcomes Following Operative Hysteroscopy for Treatment of Retained Products of Conception: Does Time from Surgery to Conception Matter?

What is the risk of developing intracavitary fluid (ICF) during ovarian stimulation in patients with an isthmocele after previous caesarean section (CS) delivery? In patients with an existing isthmocele, the risk of developing ICF during hormonal stimulation for IVF is almost 40%; therefore, special attention has to be paid to exclude fluid accumulation during stimulation and particularly at the time of transfer, in which case the reproductive outcomes of frozen embryo transfer (FET) cycles appear to be uncompromised. Lately, there is an increasing focus on the long-term impact of CS delivery on the health and future fertility of the mother. Development of an isthmocele is one of the sequelae of a CS delivery. The presence of ICF in combination with an isthmocele has been described previously, and the adverse effect of endometrial fluid on implantation is well recognised by reproductive medicine specialists. Accumulation of ICF has been previously described in patients with hydrosalpinx, less commonly in patients with polycystic ovary syndrome undergoing ovarian stimulation for IVF/ICSI, and even in some patients without any identifiable reason. Assisted reproductive techniques (ARTs) are a means to overcome infertility. Reproductive medicine specialists commonly see patients with secondary infertility with a history of having had one or more previous CS and with ultrasound confirmation of an isthmocele. However, the available data pertaining to the prevalence of intracavitary fluid during ovarian stimulation in patients with ultrasound confirmation of an isthmocele is limited. Furthermore, data on the influence of ICF in a stimulated cycle on the ART outcome of a subsequent FET cycle is scarce and merits further studies. A prospective observational exploratory study was performed in IVI Middle East Fertility Clinic, Abu Dhabi, from June 2018 to March 2019, and retrospective analysis of the reproductive outcomes was performed until July 2019. Patients with secondary infertility, defined as a minimum of 1year of infertility after a previous successful pregnancy, undergoing ovarian stimulation for IVF/ICSI and having a history of one or more previous CS with ultrasonographic visible isthmocele, were included (n= 103). Patients were monitored as a clinical routine with vaginal ultrasound examinations during ovarian stimulation for IVF/ICSI treatment. All patients included in the study were asked to complete a questionnaire regarding their previous obstetric history. Development of ICF was recorded as well as changes in the measurements of the isthmocele during the course of ovarian stimulation. Reproductive outcomes of FET cycles of the patients with an isthmocele were retrospectively compared to those of patients with infertility and without isthmocele in our clinic during the same time period. Patients with an existing isthmocele after previous CS have a risk of ~40% of developing ultrasonographic visible fluid in the endometrial cavity during the course of ovarian stimulation. Development of ICF was significantly correlated with the depth of the isthmocele on Day 2/3 (P= 0.038) and on the day of trigger (-1/-2days) (P= 0.049), circumference of the isthmocele on the day of trigger (-1/-2days) (P= 0.040), distance from the C-scar to the external os (P= 0.036), number of children delivered (P= 0.047) and number of previous CS (P= 0.035). There was a statistically significant increase in the parameters related to the size of the isthmocele during ovarian stimulation. No significant differences in the reproductive outcome (pregnancy rate and rates of biochemical and ectopic pregnancies, miscarriages and ongoing/delivered pregnancies) after FET were found between the patients with and without an isthmocele, when ICF was excluded prior to embryo transfer procedure. NA. This study was not primarily designed to investigate the causes of ICF during ovarian stimulation or to evaluate the reproductive outcomes. Further, the small number of reported reproductive outcomes may be seen as a limitation. The data highlights the need for an increased awareness on the part of reproductive medicine specialists towards the potentially adverse impact of an isthmocele on ART treatment, as there is a potential to develop intracavitary fluid during ovarian stimulation for IVF. The increase in the circumference of the isthmocele may increase embryo transfer difficulty. No funding of the study has to be reported. The authors have no competing interests. This prospective study was registered with clinicaltrials.gov. under the number NCT03518385.

Surgical and Reproductive Outcomes in Patients with Complete Septate Uterus and Cervical Anomalies after Metroplasty