Reproductive and ICSI outcomes after hysteroscopic metroplasty for T-shaped uterus, a prospective follow up study.

BACKGROUND: The incidence of uterine anomalies is approximately 0.5-4.7%. In infertile women, this rises to 6.3%. T-shaped uterine anomalies have been associated with infertility, recurrent implantation failure (RIF), and recurrent miscarriage (RM). Hysteroscopic metroplasty (HM) may improve the reproductive outcomes of such cases. STUDY OBJECTIVE: We assessed the effects of hysteroscopic metroplasty on the reproductive and in vitro fertilization (IVF) outcomes in women with T-shaped uteri. DESIGN: A prospective controlled study. SETTING: A teaching hospital. PATIENTS: The reproductive outcomes of 182 patients with primary infertility (PI), RIF, or RM who underwent hysteroscopic metroplasty to treat T-shaped uteri were prospectively analyzed. INTERVENTIONS: Between January 2017 and April 2021, hysteroscopic metroplasty was performed by a single experienced surgeon. The primary outcome was the live birth rate (either spontaneous or assisted). MEASUREMENTS AND PRINCIPAL RESULTS: In all, 182 patients who underwent bilateral, longitudinal, uterine-lateral wall incisions without complications were included. The clinical pregnancy rates after metroplasty were 50.9% (primary infertility group), 71.4% (RM group), and 39.5% (RIF group). During the 1-year follow-up, 25.5% of patients conceived spontaneously (all groups). CONCLUSION: Hysteroscopic metroplasty should be considered for women with primary infertility, RIF, and RM with T-shaped uteri.

In vitro fertilization and preimplantation genetic diagnosis outcomes in mosaic Turner's syndrome: A retrospective cohort study from a single referral center experience.

BACKGROUND: Patients with mosaic Turner syndrome who have normal phenotype and pubertal development may be diagnosed based on karyotype examination which is performed due to recurrent abortion or recurrent implantation failure; but according to the literature review, reproductive and obstetric consequences of these cases are based on case reports. There are contradictory publications on this subject recommending pre-implantation genetic testing (PGT) may be a solution to reduce the high risk for the fetus and perform normal embryo transfer. AIM: In this study, our aim was to evaluate the results of in vitro fertilization and preimplantation genetic diagnosis in patients with low-grade and high-grade mosaic Turner syndrome. METHODS: We collected data of patients between 2012 and 2018 from a single center retrospectively. The study analyzed 36 mosaic Turner syndrome patients, of whom, 10 patients were evaluated as high, 26 patients were evaluated as low-grade mosaic pattern for Turner syndrome. RESULTS: Mean age (35,46±0,87 vs. 36,2 ± 1,85) body mass index (25,26±0,74 vs. 30,8 ± 0,63) baseline follicle stimulating hormone (5,73±0,74 vs. 6,70±1,17) basal luteinizing hormone (4,78±0,43 vs. 4,92±0,99) were similar between two groups. In the high-grade mosaic Turner Syndrome patients, duration of stimulation (7,60±0,16 vs. 8,0 ± 0,28, p<0,001), total gonadotrophin dose (1540,0 ± 165,12 vs. 2046,15± 111,47, p<0,001) and the number of normal karyotype embryos was statistically significantly higher (1,58±0,17 vs. 2,00±0,55, p<0,001). The Pregnancy rates in the low-grade and high-grade mosaic Turner syndrome patients' cycles were 30,8% versus 30%, (p = 0.76) respectively. IVF results were also evaluated by the presence of triploidy were accompanying Turner syndrome or not. In the presence of one or 2 X chromosomes, none of the included in the study could achieve live birth. The most common abnormality in the embryos was monosomy and trisomy of the chromosome13. In 30% of the cases, there were 2 or 3 abnormalities present together. In embryos with 2 abnormal chromosomes, the most common 2 abnormalities were monosomy 13 and trisomy 21, while trisomy 13, trisomy X and monosomy 18 were found in 3 or more abnormalities, respectively. CONCLUSION: In vitro fertilization and Preimplantation genetic diagnose should be considered in the infertility treatment of the patient with mosaic Turner Syndrome.

The effect of hysteroscopy and conventional curretage versus no hysteroscopy on live birth rates in recurrent in vitro fertilisation failure: a retrospective cohort study from a single referral centre experience.

This retrospective cohort study aimed to evaluate the effect of hysteroscopy and endometrial scratching (ES) in patients with recurrent implantation failure (RIF) who do not have an intracavity pathology. The authors retrospectively collected data of patients between 2014 and 2019 from a single centre. The study analysed 350 unexplained RIF patients, of whom, 225 underwent hysteroscopy and endometrial scratching, and 125 did not have a hysteroscopy prior to an IVF cycle. Pregnancy rates among post endometrial scratching and no endometrial scratching cycles were 35.6% versus 27.2%, (p = .048), clinical pregnancy rates were 32.9% versus 21.6% (p = .026) and live birth rates were 26.2% versus 19.2% (p = .039). Although it is not possible to distinguish whether hysteroscopy or injury is effective in improving live birth results, the authors thought that endometrial injury with gentle conventional curettage is effective in patients with recurrent implantation failure.IMPACT STATEMENTWhat is already known on this subject? Hysteroscopy and endometrial injury improve pregnancy outcomes in IVF cycles, but definitive conclusions have been uncertain.What do the results of this study add? The study showed that endometrial injury with gentle conventional curettage during hysteroscopy significantly improved the pregnancy rates of RIF patients compared to the non-hysteroscopy group.What are the implications of these findings for clinical practice and/or further research? In cases of recurrent implantation failure, even if hysteroscopy findings are normal, endometrial scratching in the follicular phase increases pregnancy rates compared to the non-hysteroscopy group.

Is frozen embryo transfer better than fresh embryo transfer in women undergoing intracytoplasmic sperm injection over the age of thirty-five? A single referral centre experience.

Developments in embryo freezing techniques in recent years have increased the chance of pregnancy after frozen embryo transfers. In this study we aimed to compare the pregnancy outcomes between fresh (ET) and frozen-thawed embryo transfer (FET) and to evaluate the benefits of embryo freezing strategy for a woman of advanced age. A total of 513 ET cycles in women over the age of 35 years, including 397 fresh ET cycles and 116 FET cycles were reviewed. Mean age was 37.7 ± 2.91 years in FET cycles and 38 ± 2.8 in fresh cycles (p = .327). The patients undergoing FET cycles had higher oestradiol levels and progesterone levels on the day of trigger in their previous fresh cycles compared to that of fresh ET cycles (1675 pmol/L versus 991 pmol/L; 1.43 pmol/L versus 0.96 pmol/L; p < .005, respectively). Biochemical pregnancy rates (43% versus 32%; p = .048), clinical pregnancy rates (38% versus 29%; p = .030) and live birth rates (30% versus 19.6%; p = .013) were significantly higher in the FET than in the fresh ET over 35 years of age.IMPACT STATEMENTWhat is alreday known on this subject? Ovarian stimulation commonly results in the generation of more embryos than are necessary for the fresh embryo transfer. Therefore, cryopreservation and subsequent replacement of frozen-thawed embryos is an integral part of assisted reproductive technique (ART) programs. As IVF technology improved, embryo freezing was performed to allow subsequent transfer if the fresh cycle was unsuccessful.What do the results of this study add? Clinical pregnancy rates and live birth rates were found to be higher in frozen thawed embryo transfer group compared to fresh embryo transfer group over the age of 35.What are the implications of these findings for clinical practice and/or further research? Frozen thawed embryo transfer seems to be a reasonable and favourable method compared to fresh embryo transfer in patients over 35 years.

Controlled ovarian stimulation outcomes of fertility preservation procedures in newly diagnosed breast cancer patients: a retrospective study from a single-tertiary-IVF centre.

The aim of this study was to evaluate the effectiveness of controlled ovarian stimulation (COS) using the letrozole-supplemented stimulation protocol in breast cancer (BC) patients prior to their cancer treatment. Sixty-one BC patients (Stages 0-3) who were referred to a university IVF unit for fertility preservation (FP) and underwent embryo and/or oocyte cryopreservation between 2008 - 2020 were included in this retrospective study. Time intervals between breast surgery and initial fertility consultation (IFC)/completion of FP procedures were evaluated. COS outcomes were assessed and compared between the early follicular phase (EFP) and the random-start (RS) protocols. The patients' mean age was 33.3 ± 4.9 years. The mean time interval between breast surgery and IFC was 20.6 ± 11 (day, mean ± SD) and from IFC to completion of FP procedure was 14.7 ± 5.3. Overall, 9.1 ± 5.9 mature oocytes were obtained, with a peak serum oestradiol level of 388 ± 358 pg/mL. The number of oocytes obtained (11.5 ± 9.3 vs. 10.9 ± 6.9, p = .9) and maturation rates (84.3 ± 17.5% vs. 89.2 ± 11.7, p = .5) were not statistically different between the EPF and RS protocols. The study results support that oocyte or embryo freezing can be performed effectively in a limited time period with letrozole-supplemented COS protocols before the initiation of oncological treatments in breast cancer patients.Impact statementWhat is already known on this subject? Currently, embryo and oocyte freezing are considered the most established fertility preservation (FP) methods for newly diagnosed cancer patients.What do the results of this study add? This study reports the COS outcomes of newly diagnosed breast cancer patients for FP over a period of twelve years from a single IVF unit. The results support that a considerable number of oocytes can be harvested with letrozole-supplemented COS protocol, which appears to be an effective protocol for BC patients.What are the implications of these findings for clinical practice and/or further research? There is a need for additional studies evaluating long-term follow-up of patients with their pregnancy outcomes.

Evaluating the role of endometrial colour Doppler dynamic tissue perfusion measurements in in vitro fertilisation success.

The role of uterine receptivity and endometrial perfusion in in vitro fertilisation (IVF) remains unclear. In our prospective pilot study, we used a new dynamic tissue perfusion measurement method to evaluate this relationship in humans. A standard ovulation induction and embryo transfer method were applied to all the volunteers. On the day of embryo transfer, dynamic images of the uterus were recorded using colour Doppler ultrasound, and these images were uploaded onto PixelFlux Chameleon Software (GmbH, Münster, Germany). After determining the region of interest (ROI), the average velocity, intensity, and area values for all coloured pixels in the ROI, the tissue resistance index (RI) and the tissue pulsatility index were calculated. Endometrial thickness, morphology and dynamic endometrial perfusion parameters were compared between the clinically pregnant and non-pregnant groups. Endometrial thickness, morphology values and endometrial dynamic tissue perfusion measurements were similar between the groups. This study compared perfusion parameters between clinically pregnant and non-pregnant patients by accurately calculating endometrial tissue perfusion using standard software to establish its relationship with implantation success in IVF treatment.IMPACT STATEMENTWhat is already known about this subject? The relationship between IVF success, endometrial receptivity and perfusion is known. Clear valuations of endometrial receptivity require an endometrial biopsy which may cause endometrial damage to the actual IVF cycle. This problem has led researchers to conduct non-interventional studies. Studies have revealed the value of endometrial thickness, pattern and Doppler examination of endometrial uterine arteries in predicting the success of IVF treatment.What do the results of this study add? This prospective pilot study is the first one to use this programme in humans to evaluate uterine receptivity in IVF. Successful results can be obtained by using computer programmes in tissues where perfusion parameters cannot be measured using traditional colour Doppler ultrasonography. Revealing the relationship between tissue perfusion and IVF success will be more effective and accurate with the development of software technologies.What are the implications of these findings for clinical practice and/or further research? To increase the success of IVF treatment, current and new technological developments, as well as imaging methods should continue to be tested.

Assisted reproductive treatment outcomes of women with endometriomas: Either with or without previous ovarian surgery.

OBJECTIVE: The present study aimed to evaluate and compare the assisted reproductive technique (ART) outcomes of women with endometriomas either with or without prior endometrioma surgery. MATERIALS AND METHODS: A total of 122 women with endometriomas underwent intracytoplasmic sperm injection-embryo transfer (ICSI-ET) at a tertiary IVF Center, between 2014 and 2019, were included in this retrospective study. Of this group, 38 patients had recurrent endometriomas and 84 patients had primary endometrioma without a previous endometrioma surgery. The outcomes of ART treatment including cancellation rates before ET, numbers of oocytes obtained, implantation, clinical pregnancy and live birth rates were compared between the groups. A logistic regression model including potential confounders as age and presence of male factor infertility was used to evaluate the possible effect of recurrent endometriomas on the live birth. RESULTS: The baseline characteristics of the groups were similar. The poor ovarian response rate, defined as the harvest of fewer than four oocytes, was identified in 35.7% and 42.1% of primary and recurrent endometrioma groups, respectively. The implantation (27.2 ± 42.7% vs 24.1 ± 41.4%, P = .74), clinical pregnancy/ET (30.9% vs 27.6%, P = .93 ) and live birth rates/ET (22.1% vs 17.2%, P = .79) CONCLUSION: The ART outcomes of patients with primary and recurrent endometriomas do not seem different in terms of response to ovarian stimulation and live birth rates after ICSI. These results may indicate that the recurrence of the endometrioma might not have a further detrimental effect on ART outcome than the disease itself.

In-Vitro Fertilization Outcome Predictors in Women With High Baseline Follicle-Stimulating Hormone Levels: Analysis of Over 1000 Cycles From A Tertiary Center.

OBJECTIVE: The present study aimed to evaluate reproductive outcomes and determine the predictors of clinical pregnancy and live birth in women with elevated baseline follicle-stimulating hormone (FSH) levels, who have undergone intracytoplasmic sperm injection (ICSI) treatment. METHODS: This retrospective study included 1011 ICSI cycles of women with high baseline FSH levels (> 10 IU/L), from a tertiary university IVF center between 2010 and 2015. Logistic regression analysis was performed to evaluate the prognostic factors of clinical pregnancy and live birth. RESULTS: Among the 1011 ICSI cycles, the clinical pregnancy and live birth rates per oocyte retrieval were 19.5% and 14.3%, respectively. The live birth rates were 21.1% and 1.7% in women aged ≤30 years and those aged ≥40 years, respectively. In addition, the live birth rate was 1.47-fold higher in women from whom >3 oocytes were retrieved, compared to those from whom ≤3 oocytes were retrieved (p=0.047). Logistic regression analysis indicated that the age categories ≤30y, 36-39y and ≥40y, level of baseline FSH (≥20 IU/L) and the ovarian response (≤3 or >3 oocytes retrieved) were significantly associated with live birth. CONCLUSIONS: Our study indicated that age, baseline FSH level, and ovarian response are independent predictive factors for clinical pregnancy and live birth among women with baseline FSH levels >10 IU/L.

Live birth after frozen-thawed embryo transfer: which endometrial preparation protocol is better?

OBJECTIVE: To compare the clinical outcomes of modified natural cycle (mNC) and artificial cycle (AC) protocols for frozen embryo transfers. MATERIAL AND METHODS: A total of 490 frozen-thawed autologous embryo transfer cycles, performed in a single tertiary IVF center, between January 2015 and September 2017, were retrospectively analyzed. Of these, 214 cycles were performed after mNC and 276 cycles were performed after gonadotrophin-releasing hormone (GnRH) agonist plus sequential estrogen and progestin priming protocol. The primary outcome was live birth and secondary outcomes were clinical pregnancy, implantation and miscarriage rates. Multivariate regression analysis was used to adjust covariates on clinical outcome. RESULTS: The rates of live birth (33.6 % vs. 29.3 %, respectively), clinical pregnancy (40.2 % vs. 36.6 %, respectively), implantation (32.3 % vs. 28.5 %, respectively), and miscarriage (5.1 % vs. 6.9 %, respectively) were not different between the mNC and AC groups. Multivariate analysis also showed that the method for endometrial preparation had no significant effect on clinical pregnancy and live birth. The adjusted odds ratios (OR) of live births and clinical pregnancies were 0.97 (95 % CI 0.64-1.48) and 0.98 (95 % CI 0.65-1.46) for the AC compared to mNC group. However, there was a significant difference between mNC and AC in cycles in which double embryo transfer was performed. The live birth (48 % vs. 31.4 %P= 0.01) and clinical pregnancy rates (53.9 % vs. 38.8 %, P= 0.02) were significantly higher in the mNC group than the AC group for double embryo transfers. CONCLUSION: The live birth and clinical pregnancy rates are comparable between mNC and AC with GnRH agonists in frozen thawed embryo transfer cycles. In ovulatory patients with planned double embryo transfer, mNC can be considered. Further well-designed prospective studies are needed to confirm our results.

A Rare Case of Bilateral Tubal Ectopic Pregnancy Following Intracytoplasmic Sperm Injection-Embryo Transfer (ICSI-ET).

Bilateral tubal ectopic pregnancy is a very rare form of ectopic pregnancy. The incidence is higher in women undergoing assisted reproductive techniques or ovulation induction. We report the case of bilateral tubal ectopic pregnancy. The patient was 30 years old and had a 3-year history of infertility; she was referred to the in-vitro fertilization (IVF) program because of tubal factor infertility. A pregnancy resulted from the transfer of two embryos during an artificial cycle. Despite the increase in ß-hCG values during the follow-up, 22 days after the embryo transfer, the ß-hCG levels were 2,408 U/L and the serum progesterone (P4) level was 10.53 ng/ml. After application with methotrexate, ß-hCG levels did not decrease effectively. Moreover, the sonographic screening revealed a suspicious bilateral tubal focus for ectopic pregnancy. A mini-laparotomy was performed and a bilateral tubal pregnancy was found. In the case of unilateral tubal pregnancy after the transfer of two embryos, the situation of the other tube should be systematically checked and ß-hCG levels should be monitored.

A Rare Case of Bilateral Tubal Ectopic Pregnancy Following Intracytoplasmic Sperm Injection-Embryo Transfer (ICSI-ET)

Abstract Bilateral tubal ectopic pregnancy is a very rare form of ectopic pregnancy. The incidence is higher in women undergoing assisted reproductive techniques or ovulation induction. We report the case of bilateral tubal ectopic pregnancy. The patient was 30 years old and had a 3-year history of infertility; she was referred to the in-vitro fertilization (IVF) program because of tubal factor infertility. A pregnancy resulted from the transfer of two embryos during an artificial cycle. Despite the increase in β-hCG values during the follow-up, 22 days after the embryo transfer, the β-hCG levels were 2,408 U/L and the serum progesterone (P4) level was 10.53 ng/ml. After application with methotrexate, β-hCG levels did not decrease effectively. Moreover, the sonographic screening revealed a suspicious bilateral tubal focus for ectopic pregnancy. A mini-laparotomy was performed and a bilateral tubal pregnancy was found. In the case of unilateral tubal pregnancy after the transfer of two embryos, the situation of the other tube should be systematically checked and β-hCG levels should be monitored.

In vitro fertilization-induced pregnancies predispose to gastroesophageal reflux disease.

BACKGROUND: Women conceiving following in vitro fertilization (IVF) likely have a variety of risk factors that predispose them to gastroesophageal reflux disease (GERD) in the future. OBJECTIVE: We aimed to investigate whether pregnancy through IVF may predispose to subsequent GERD compared with pregnancies without IVF. We also evaluate whether twin IVF pregnancies lead to additional risk for having GERD compared with singleton IVF pregnancies. METHODS: A validated reflux questionnaire was administered to 156 women with singleton (n = 102) or twin (n = 54) IVF birth (IVF group) and 111 women with a naturally conceived singleton birth (control group). All women included in the study were primiparas who had given birth at least 1 year prior to data collection. The diagnosis of GERD was based on the occurrence of typical symptoms (heartburn, regurgitation, or both) at least once a week. RESULTS: The prevalence of GERD was 13.5% and 4.5% in IVF and control groups (p = 0.015); in the IVF group, this was slightly higher, but not statistically significant, in women with twin compared with singleton pregnancies (14.8% vs. 12.7%, p = 0.749). Logistic regression analysis showed that IVF was strongly associated with subsequent GERD (OR, 3.30; 95% CI 1.20-9.04; p = 0.02). CONCLUSION: The risk of developing GERD at least 1 year after delivery increased following IVF. Long-term follow-up studies are required to determine whether therapy during pregnancy can prevent this risk.

Comparison of montelukast and cabergoline for prevention of ovarian hyperstimulation syndrome: in an experimental rat model.

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication that can occur during assisted reproductive techniques. The aim of this study is to investigate the effects of the leukotriene receptor antagonist (montelukast) treatment in prevention of OHSS and compare to cabergoline treatment. Twenty-four immature female Wistar rats were assigned to four groups. Group 1 was the control group. In the remaining three groups, OHSS was induced through ovarian stimulation with gonadotropins. No treatment was given to Group 2. Group 3 was administered a low-dose 100 mg/kg cabergoline treatment and Group 4 was received 20 mg/kg montelukast. Body weight, ovarian weight, vasculary permability (VP), peritoneal fluid vascular endothelial growth factor (VEGF) values and VEGF immune-expression were compared between the groups. Both cabergoline and montelukast prevented progression of OHSS compared to the OHSS group. Body weight, ovarian weight, VP, peritoneal fluid VEGF values and VEGF expression were significantly lower in both cabergoline- and montelukast-treated rats than in those not treated OHSS group. In conclusion, montelukast is an effective option for prevention of OHSS, as well as cabergoline. Montelukast may be a new treatment option to prevent and control the OHSS.

Diagnosis of pregnancy after conservative management for adnexal torsion due to ovarian hyperstimulation in the same cycle.

We report a case of right adnexal torsion during the embryo implantation period of an IVF/ICSI cycle. A 26-yearold woman who diagnosed as primary infertility was included in an IVF/ICSI program. In the following period right adnexal torsion occurred at the sixth day of the embryo transfer. Laparoscopic detortion was successfully performed with preserving the adnexia. The patient had positive pregnancy test in the subsequent week.

Fertility preservation by ovarian stimulation and oocyte cryopreservation in a 14-year-old adolescent with Turner syndrome mosaicism and impending premature ovarian failure.

OBJECTIVE: To report a novel approach to fertility preservation in adolescents with Turner syndrome mosaicism by repeated controlled ovarian stimulation and oocyte cryopreservation. DESIGN: Case report. SETTING: Academic reproductive medicine center. PATIENT(S): Fourteen-year-old adolescent diagnosed with Turner syndrome mosaicism. INTERVENTION(S): Two cyles of controlled ovarian stimulation and oocyte cryopreservation within 1 year. MAIN OUTCOME MEASURE(S): Recovery of oocytes after controlled ovarian stimulation and oocyte cryopreservation. RESULT(S): Eleven oocytes were retrieved, of which eight were mature and three were immature during the first cycle. One year later, four mature and three immature oocytes were retrieved after a treatment cycle with even higher gonadotropin doses. All oocytes were cryopreserved by vitrification. CONCLUSION(S): Controlled ovarian stimulation and oocyte cryopreservation may be an option for fertility preservation in selected adolescents with Turner syndrome mosaicism and impending ovarian failure.

Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy.

CONTEXT: Women with breast cancer are not typically offered embryo or oocyte cryopreservation to preserve their fertility before chemotherapy because of the potential risks associated with high estrogen levels arising from ovarian stimulation. OBJECTIVE: We aimed to determine whether the combination of an aromatase inhibitor with gonadotropin treatment in breast cancer patients produces comparable results to standard in vitro fertilization (IVF), without a significant increase in estradiol levels and delay in the initiation of chemotherapy. PATIENTS AND METHODS: Stages I-IIIA breast cancer patients (n = 47) received 5 mg/d letrozole and 150-300 IU FSH to cryopreserve embryos or oocytes. Age-matched retrospective controls (n = 56) were selected from women who underwent IVF for tubal disease. RESULTS: Whereas letrozole and FSH stimulation resulted in significantly lower peak estradiol levels (mean +/- sd 483.4 +/- 278.9 vs. 1464.6 +/- 644.9 pg/ml; P < 0.001) and 44% reduction in gonadotropin requirement, compared with controls, the length of stimulation, number of embryos obtained, and fertilization rates were similar. The human chorionic gonadotropin administration criteria had to be adjusted to 20 mm after letrozole stimulation, compared with 17-18 mm in the controls. The mean delay from surgery to cryopreservation was 38.6 d, with 81% of all patients completing their IVF cycles within 8 wk of surgery. CONCLUSION: Ovarian stimulation with letrozole and FSH appears to be a cost-effective alternative for fertility preservation in breast cancer patients with reduced estrogen exposure, compared with standard IVF. If patients are referred promptly, they may undergo embryo or oocyte cryopreservation without a delay in chemotherapy.