Initiating luteal phase support with sc progesterone based on low serum progesterone on the transfer day in true natural cycle frozen embryo transfers.

Introduction: Concerning contemporary in-vitro fertilisation (IVF) practice, the use of frozen embryo transfer (FET) cycles has become more common than fresh transfers. Natural cycle (NC), programmed artificial cycle and mild stimulation cycle are primary endometrium preparation cycles. Monitoring serum progesterone levels in FET cycles are in the scope of current research focus. Low progesterone levels on the day of embryo transfer is presumed to negatively affect pregnancy outcomes, while progesterone supplementation may improve pregnancy rates. The purpose of our trial is to evaluate whether initiating subcutaneous (SC) progesterone supplementation on the day of embryo transfer when serum progesterone levels are below 10 ng/mL in tNC-FET will result in pregnancy rates comparable to those of patients with sufficient serum progesterone. Methods: Retrospective single centre study was conducted between August 2022 and April 2023 with 181 tNC-FETs. Patients were separated into groups according to serum progesterone concentrations (≥10 ng/mL and <10 ng/mL) on embryo transfer (ET) day. S.c progesterone (25 mg) was given on the day of ET when serum progesterone was <10 ng/mL, continuing until the 10th gestational week. Blood samples for pregnancy tests were collected 12 days after ET. Outcome parameters were pregnancy rate, clinical pregnancy rate (CPR), miscarriage rate, multiple pregnancy rate, biochemical pregnancy, and ongoing pregnancy rate (OPR). Results: About half (49.7%) had adequate progesterone concentrations (≥10ng/mL) on ET day. There was no significant difference between the groups regarding positive pregnancy test, OPR, multiple pregnancies, and miscarriage rates (57.8% versus 52.7%; 34.4% versus 29.7%, 1.1% versus 2.2%; 7.8% versus 5.5%; respectively, for progesterone concentrations on ET day ≥10 ng/mL and <10 ng/mL). With 55.2% of transfers leading to clinical pregnancy, significant differences emerged in biochemical pregnancy and CPR (3.3% vs 12.1%, P=0.02; 54.4% vs 40.7%, P=0.03, for ≥10 ng/mL and <10 ng/mL progesterone concentrations on ET day). Discussion: This study indicates that nearly half of the tNC-FETs may need luteal phase support due to low progesterone. However, 25 mc sc progesterone rescued the luteal support and yielded similar OPR as compared to normal progesterone group. Further studies are needed for understanding optimal progesterone levels, supplementation effectiveness, and potential benefits of earlier supplementation in FETs.

Oral, vaginal or intramuscular progesterone in programmed frozen embryo transfer cycles: a pilot randomized controlled trial.

RESEARCH QUESTION: What should be the optimal route of luteal support in programmed frozen embryo transfer (FET) cycles? DESIGN: This was a randomized, parallel, phase IV pilot trial with three groups of women undergoing FET along with hormone replacement therapy for endometrial preparation at a tertiary private IVF centre (NCT03948022). Women with at least one autologous cryopreserved blastocyst were included. After preparing the endometrium with oestradiol, 151 women were randomly assigned to one of the following three progesterone arms before embryo transfer: oral (10 mg) dydrogesterone (DYD), total daily dose 40 mg (n = 52); 8% (90 mg) progesterone vaginal gel (VAG), total daily dose 180 mg (n = 55); or intramuscular progesterone (IMP) 50 mg/ml in oil, total daily dose 100 mg (n = 44). One or two vitrified-warmed blastocysts were transferred after 5 days' progesterone support. RESULTS: Baseline demographic features and embryological data were comparable among the groups. Ongoing pregnancy rates (40.4%, 38.2% and 45.5% in the DYD, VAG and IMP arms; P = 0.76) and live birth rates (40.4%, 38.2% and 43.2% in the DYD, VAG and IMP arms, P = 0.61) were statistically similar. Biochemical pregnancy rates and clinical miscarriage rates were also statistically similar among the groups. Significantly more patients with at least one side effect and moderate-to-severe side effects were documented in the IMP arm than the other groups (P < 0.001). CONCLUSIONS: Treatment with 40 mg/day oral DYD, 180 mg/day progesterone VAG gel or 100 mg/day IMP revealed similar reproductive outcomes in programmed FET cycles. Side effects were significantly more frequent in the IMP arm.

Dual Trigger with hCG Plus GnRHa for Final Oocyte Maturation in PGT-A Cycles Results in Similar Euploidy Rates when Compared to hCG-Only Trigger.

Factors that may have an effect on euploidy rate of blastocysts have been investigated thoroughly in the literature. We aimed to assess whether dual trigger alters the ploidy chance of a blastocyst in preimplantation genetic screening for aneuploidy (PGT-A) cycles. This retrospective cohort study was conducted in a total of 385 PGT-A cycles at a single tertiary center for various indications. Final oocyte maturation was triggered using human chorionic gonadotropin (hCG) or the combination of hCG and gonadotropin-releasing hormone agonists (GnRHa) (dual trigger). Participants were divided based on triggering method and all demographic and clinical characteristics of the patients were compared. Final oocyte maturation was triggered in 143 cycles with hCG (37.1%), and in 242 cycles with dual trigger (62.9%). The duration of stimulation was shorter in the dual trigger arm compared to the hCG trigger group (10.0 ± 1.6 vs. 9.4 ± 1.4 days, p ≤ .001). Euploidy rates per blastocyst tested were 23.4% and 26.1% respectively for hCG and dual trigger groups without significance. Similar rates of euploidy were noted, even after age stratification. There was no significant difference between the groups regarding positive pregnancy result and ongoing pregnancy rates (p = .779 vs. p = .188). Although dual triggering, compared to hCG triggering, does not provide an additional superiority on blastocyst euploidy rate, further studies in women with different infertility etiology are needed to specifically evaluate the impact of triggering method on ploidy rates.

Fertility outcomes after preconceptional laparoscopic abdominal cerclage for second-trimester pregnancy losses.

OBJECTIVE(S): Cervical incompetence is an important cause of recurrent pregnancy loss, typically presenting in the second trimester with silent cervical dilation and premature delivery of the fetus. We aimed to evaluate the conception rate and time to conception or failure to conceive after preconceptional laparoscopic abdominal cerclage (LAC). STUDY DESIGN: We conducted this retrospective observational cohort study at a tertiary referral center. Patients who underwent LAC in the nonpregnant state for a second-trimester pregnancy loss between June 2012 and February 2020 were included. RESULTS: The subjects were 40 patients with a history of one or more second-trimester pregnancy losses despite the placement of vaginal cerclage, who had undergone LAC before contemplating a future pregnancy. The mean number of second-trimester pregnancy losses before LAC was two per woman. The ages of the women at the time of cerclage ranged from 21 to 42 years. The time to pregnancy, which was the primary outcome of the study, was determined as the number of menstrual cycles before the patient became pregnant after LAC and the number of cycles needed for the patient to achieve her latest pregnancy before LAC. Of the 40 women, 22.5 % were noted during the LAC operation to have a pelvic peritoneal pathology that might have affected fertility, and all such pathologies were treated concomitantly during the procedure. Spontaneous pregnancy rates before and after LAC were 96.4 % and 89.3 % (p = 0.299), and times to pregnancy before and after LAC were 6.3 ± 8.4 and 6.6 ± 8.1 cycles (p = 0.897). Neither difference was statistically significant. In more than 84 % of patients who became pregnant after LAC, pregnancy was sustained to the stage of viability. CONCLUSION(S): In patients with cervical incompetence, LAC is a very effective intervention to sustain pregnancy to the stage of viability. If placed during the preconceptional period, it does not delay achieving pregnancy and does not have a negative impact on the chances of conception. This may be reassuring to women undergoing this procedure before they achieve a pregnancy.

The Preventive Effect of Curcumin on the Experimental Rat Epidural Fibrosis Model.

OBJECTIVE: The aim of the study was to evaluate the effect of systemically administrated curcumin on the prevention of peridural fibrotic tissue and adhesion formation in a rat laminectomy model. METHODS: Thirty-two Wistar albino rats were randomly selected and equally divided into 4 groups as follows: negative control group (group I) did not undergo operation; positive control group (group II) underwent laminectomy without treatment; group III (low-dose curcumin; 100 mg/kg); and group IV (high-dose curcumin; 200 mg/kg). Curcumin was administered intraperitoneally per day for 7 days after surgery starting from day 0. Twenty-eight days after surgery, T12 and L4 vertebral columns, paraspinal tissues, and epidural scar tissue were dissected en bloc and prepared for histopathologic examinations. All specimens were examined for inflammation, epidural fibrosis (EF), foreign body reaction, medulla spinalis retraction, granulation tissue, and arachnoid involvement. A Kruskal-Wallis test followed by a Dunn multiple comparison test were used for statistical analysis, and a P value <0.05 was considered as statistically significant. RESULTS: Curcumin treatment significantly reduced inflammation, foreign body reaction, granulation tissue formation, medulla spinalis retraction, and EF formation compared with positive control group (P < 0.05); however, no significant differences were found between the 2 groups that received different doses of curcumin. CONCLUSIONS: The results of the present study showed that systemic administration of curcumin was effective in reducing EF formation, inflammation, granulation tissue formation, medulla spinalis retraction, and foreign body reaction in the laminectomy area. Our results suggest that antiinflammatory activities of curcumin are beneficial for attenuation of EF formation.

Analysing the blood-stemming effect of Ankaferd Blood Stopper in medulla spinalis surgery

Background/aim: The aim of this study was to investigate the possible toxicity of the Ankaferd Blood Stopper (ABS) on the neural system. Materials and methods: Thirty Sprague Dawley rats were randomized into ABS (n: 15) and control (n: 15) groups. Following the anaesthetic induction, total laminectomy was performed to the lower thoracic, and upper lumbar areas in both groups and medulla spinalis was exposed. Two myelotomies were performed on the medulla spinalis. One millilitre ABS was applied to the incision site in the ABS group, and one millilitre 0.9% saline solution was applied in the control group. Rats were observed for 15 days regarding general behaviour, neurological signs, mobility, and signs of infection. Sixteen days later, all rats were decapitated under anaesthesia. Medulla spinalis was removed en bloc from all rats and was stained with Heamatoxylin & Eosin and luxol fast blue. Results: There was no significant difference between the ABS group and the control group regarding oedema, gliosis, the intensity of inflammatory cells, the presence of neuronal degeneration, neuron counts, and myelin degeneration. Conclusion: No clinical or histopathological evidence for the neurotoxic effect of the ABS was observed in the present study. Our findings might precipitate the use of ABS on human subjects regarding medulla spinalis surgery.

The histopathological and stereological assessment of the effect of topically administered leptin on cerebral vasospasm in an experimental subarachnoid hemorrhage model

Background/aim: Cerebral vasospasm is a term that refers to prolonged, slowly progressing but reversible pathological narrowing of cerebral arteries occurring several days after subarachnoid hemorrhage (SAH), usually accompanied by a decrease in perfusion distal to the affected artery. Leptin is an endogenous polypeptide hormone that can be carried freely and bound to protein in the blood. Materials and methods: We investigated the superiority of topical application of leptin that may make a contribution to the development of new treatment modalities for unconscious patients in brain injury intensive care units and its preventive effect, which is considered to have multifactorial pathogenesis on cerebral vasospasm occurring after SAH via stereological studies of the basilar artery. Results: When mean serum leptin levels of the groups were compared, statistically significant differences were observed between the control and topical leptin-treated groups in favor of the treated groups with respect to serum leptin levels (P < 0.05). In the topical leptin-applied group, a significant difference in favor of vasodilatation was observed in the measurements of the basilar artery luminal area (P < 0.05). Conclusion: In accordance with the results, the topical administration of leptin can be used in the prevention of vasospasm, especially in unconscious patients with subarachnoid hemorrhage.

Outcomes of Micro-Dissection TESE in Patients with Non-Mosaic Klinefelter's Syndrome without Hormonal Treatment.

BACKGROUND: Klinefelter syndrome (KS) is the most common sex chromosomal disorder in males and historically patients have been labeled as sterile. After the introduction of microdissection testicular sperm extraction (micro-TESE), successful sperm retrievals for intracytoplasmic sperm injection (ICSI) have been reported. MATERIALS AND METHODS: A retrospective study was undertaken on ten patients with non-mosaic KS undergoing micro-TESE for ICSI. The testicular volume and FSH and LH levels of each patient were measured. Karyotypes were confirmed by analyzing peripheral lymphocyte metaphases. Physical examination of the external genitalia was performed in all patients to rule out any co-existing anomaly. Micro-TESE was performed in order to investigate the presence of seminiferous tubules which may contain spermatozoa. When testicular spermatozoa were found in micro-TESE, ICSI was performed. Embryos were evaluated for further development. Fertilization was considered to have occurred after the visualization of the two pro-nuclei stage of the oocyte 24 hours after the intracytoplasmic injection of the motile spermatozoa. Pregnancy was confirmed by visualization of an intrauterine gestational sac under ultrasonographic examination. RESULTS: Testicular biopsy revealed motile spermatozoa in 6 of 9 patients (66.6 %). Fertilization rate per embryo-transfer was 40%. One patient was able to conceive and fathered a healthy boy weights 3410 g at the 39(th) week of gestation. CONCLUSION: Retrieval of testicular spermatozoa by micro-TESE is possible for azoospermic men with KS when assisted reproductive techniques are applied. For patients with KS who want to conceive, assisted reproductive techniques (ART) should be recommended.

Concentrations of inflammatory cytokines and the outcome in ICSI cycles.

UNLABELLED: The aim of this study was to measure circulating and intrafollicular concentrations of three inflammatory cytokines from women undergoing ovarian stimulation in order to determine their prognostic value in the outcome of intracytoplasmic sperm injection/embryo transfer cycles. MATERIALS AND METHODS: A total of 72 women following ovarian stimulation and intracytoplasmic sperm injection were included. Blood serum samples were drawn at the day of chorionic gonadotropin administration. Follicular fluids were collected at the day of oocyte retrieval. The total fractions of tumor necrosis factor alpha, interleukin (IL)-1beta and IL-6 were measured with commercially available immunoassays. RESULTS: The concentrations of IL-1beta, both in serum and follicular fluids, were significantly different between ICSI cycles that resulted in pregnancy and those that failed. The concentrations of the other two cytokines did not significantly differ between successful and unsuccessful cycles. CONCLUSION: The circulating and intrafollicular concentrations of IL-1beta seem to be related to the pregnancy outcome in ICSI cycles of healthy women.

Transvaginal ultrasonographic assessment of the endometrium in asymptomatic, postmenopausal women using different HRT regimens containing tibolone or estrogen.

OBJECTIVE: To assess the effects of hormone replacement therapy (HRT) on endometrial thickness as measured by transvaginal ultrasonography in asymptomatic, postmenopausal women. STUDY DESIGN: Between 1997 and 2001, 307 women who had no risk factors for endometrial cancer or abnormal vaginal bleeding were enrolled in a study. Patients received 1 of the following HRT modalities: (1) oral equine HRT modalities: (1) oral equine estrogen, (2) oral 17beta-estrogen, (3) transdermal 17beta-estrogen, or (4) oral tibolone. All women taking estrogens were also taking a progestin. Only the patients with endometrial thickness >7 mm underwent endometrial biopsy while taking HRT. RESULTS: Although we observed an increase in serum estrogen levels as compared to the levels before tibolone therapy, changes in endometrial thickness were not statistically significant in patients taking tibolone. CONCLUSION: Endometrial thickness with tibolone closely mimics the naturally atrophic postmenopausal state. Thus, tibolone is suggested for those postmenopausal women who have concerns about HRT.

Evaluation of leptin, interleukin-1beta, tumor necrosis factor-alpha and vascular endothelial growth factor in serum and follicular fluids of women undergoing controlled ovarian hyperstimulation as prognostic markers of ICSI outcome.

BACKGROUND: Cytokines play an important but controversial role during ovarian folliculogenesis for the development of mature and fertilizable oocytes. In this study, leptin, interleukin-1beta (IL1beta), tumor necrosis factor-alpha (TNFalpha) and vascular endothelial growth factor (VEGF) in serum and follicular fluids (FF) of women undergoing ovarian hyperstimulation were evaluated as prognostic markers of the outcome of intracytoplasmic sperm injection (ICSI) cycles. MATERIALS AND METHODS: Ninety-five ICSI cycles were included in the study. The cytokines were measured in serum and FF samples with enzyme immunoassay methods. RESULTS: The cytokine concentrations in serum were not significantly correlated with the cytokine concentrations in FFs. Serum IL1beta was inversely-correlated with the number of retrieved oocytes. Serum TNFalpha was negatively-correlated with fertilization rate. In FFs, TNFalpha was positively-correlated with leptin. Leptin and VEGF in FFs were negatively-associated with pregnancy outcome. CONCLUSION: Leptin and VEGF concentrations in FFs may serve as prognostic markers of success after ovarian hyperstimulation and ICSI.