Serum progesterone levels greater than 32.5 ng/ml on the day of embryo transfer are associated with lower live birth rate after artificial endometrial preparation: a prospective study.

BACKGROUND: Previous observational studies have highlighted the negative effects of serum hormone levels at the minimum threshold during frozen embryo transfer (FET) cycles. However, still the questions regarding the maximum threshold level, and the highest allowed dosage of hormonal medications remain unresolved. The present study was conducted to determine whether there is any relationship between the serum progesterone and estradiol levels on the day of ET, and live birth rate (LBR) in patients receiving HRT in FET cycles. METHODS: In this prospective cohort study, eligible women who were undergoing their first or second FET cycles with the top graded blastocyst stage embryos were included. All patients received the same HRT regimen. FET was scheduled 5 days after administration of the first dosage of progesterone. On the morning of ET, 4-6 h after the last dose of progesterone supplementation, the serum progesterone (P4, ng/ml) and estradiol (E2, pg/ml) levels were measured. RESULTS: Amongst the 258 eligible women that were evaluated, the overall LBR was 34.1 % (88/258). The serum P4 and E2 values were divided into four quartiles. The means of women's age and BMI were similar between the four quartiles groups. Regarding both P4 and E2 values, it was found that the LBR was significantly lower in the highest quartile group (Q4) compared with the others, (P = 0.002 and P = 0.042, respectively). The analysis of the multivariable logistic regression showed that the serum level of P4 on ET day, was the only significant predictive variable for LBR. The ROC curve revealed a significant predictive value of serum P4 levels on the day of ET for LBR, with an AUC = 0.61 (95 % CI: 0.54-0.68, P = 0.002). The optimum level of serum P4, with 70 % sensitivity and 50 %specificity for LBR, was 32.5 ng/ml. CONCLUSIONS: The present study suggests that a serum P4 value at the maximum threshold on the day of FET is associated with reduced LBR following blastocyst transfer. Therefore, measuring and monitoring of P4 levels during FET cycles might be necessary. However, the results regarding the necessity for the screening of serum E2 levels before ET, are still controversial, and further prospective studies are required.

The Value of Routine Hysteroscopy before the First Intracytoplasmic Sperm Injection Treatment Cycle.

BACKGROUND/AIMS: To assess uterine cavity with office hysteroscopy in order to diagnose and treat pathologies in patients who have started their first intracytoplasmic sperm injection (ICSI) cycles and evaluate its impact on pregnancy rate. METHODS: A number of 220 infertile women scheduled for ICSI participated in this prospective randomized study. They were randomly divided into 2 equal groups. Group I (intervention) underwent office hysteroscopy before starting assisted reproductive techniques (ART) cycle. Group II (control) started ART cycles without office hysteroscopy. All women had normal transvaginal ultrasonography and hysterosalpingography. The detected intrauterine abnormalities were treated during hysteroscopy. Four weeks after embryo transfer, ultrasonography was done for detecting clinical pregnancy. RESULTS: Abnormal findings were seen in hysteroscopy in 22.7% of the intervention group. The pregnancy rate in the intervention group (48.20%) was significantly higher than that in the control group (38.60%; p = 0.004). CONCLUSION: Routine office hysteroscopy before ICSI cycles provides direct evaluation of uterine cavity. Also, pregnancy rate improves after correction of endometrial cavity abnormalities.

Enhancing endometrial receptivity in FET cycles: exploring the influence of endometrial and subendometrial blood flow along with endometrial volume.

Introduction: Fetal health and a receptive and healthy endometrium are two essential factors in achieving successful implantation. If the endometrium is unreceptive, postponing the transfer cycle to a suitable time can enhance the chances of pregnancy. This study aims to assess the impact of endometrial and sub-endometrial blood flows measured by Doppler ultrasound, as well as endometrial volume, on endometrial receptivity in frozen embryo transfer (FET) cycles. Methods: 112 patients with a mean age of 33.93 ± 4.93 years underwent in vitro fertilization (IVF). Serum ß-hCG level was used to confirm pregnancy, and among the participants, 50 (44.6%) achieved pregnancy after IVF. Results: The study results revealed a significant difference in endometrial blood flow between the pregnant and non-pregnant groups, with a higher pregnancy rate observed in participants exhibiting multi-focal and spare endometrial blood flows (p < 0.05). Furthermore, there was a notable association between endometrial blood flow and pregnancy outcome, as indicated by higher ongoing pregnancy rates in those with multi-focal and spare endometrial blood flows (p < 0.05). However, no significant differences were observed in endometrial variables such as volume, length, width, thickness, and pattern between the pregnant and non-pregnant groups. Additionally, contextual parameters showed no significant relationship with pregnancy outcome (p > 0.05). The study also found that endometrial measurement indices did not have a significant impact on pregnancy outcomes, with no significant differences observed between the groups (p > 0.05). Conclusion: In conclusion, endometrial blood flow is crucial for a successful pregnancy after IVF, while the predictive value of the endometrial volume is limited for pregnancy outcomes.

Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial.

BACKGROUND: This study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrome (PCOS). METHODS: Fifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The primary outcome was OS in follicular fluid (FF). The secondary outcome involved assessing gene and protein expression related to mitochondrial biogenesis, mitochondrial DNA (mtDNA) copy number, and adenosine triphosphate (ATP) content in granulosa cells (GCs). ART outcomes were evaluated at the end of the trial. RESULTS: Resveratrol significantly reduced the total oxidant status (TOS) and oxidative stress index (OSI) in FF (P = 0.0142 and P = 0.0039, respectively) while increasing the total antioxidant capacity (TAC) (P < 0.0009). Resveratrol consumption also led to significant increases in the expression of critical genes involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and mitochondrial transcription factor A (TFAM) (P = 0.0032 and P = 0.0003, respectively). However, the effect on nuclear respiratory factor 1 (Nrf-1) expression was not statistically significant (P = 0.0611). Resveratrol significantly affected sirtuin1 (SIRT1) and PGC-1α protein levels (P < 0.0001 and P = 0.0036, respectively). Resveratrol treatment improved the mtDNA copy number (P < 0.0001) and ATP content in GCs (P = 0.0014). Clinically, the resveratrol group exhibited higher rates of oocyte maturity (P = 0.0012) and high-quality embryos (P = 0.0013) than did the placebo group. There were no significant differences between the groups in terms of chemical or clinical pregnancy rates (P > 0.05). CONCLUSIONS: These findings indicate that resveratrol may be a promising therapeutic agent for patients with PCOS undergoing assisted reproduction. TRIAL REGISTRATION NUMBER: http://www.irct.ir ; IRCT20221106056417N1; 2023 February 09.

The Impact of Growth Hormone Co-Treatment Duration on Outcomes in IVF/ICSI Cycles Among Poor Ovarian Responders.

Background: The efficiency of in vitro fertilization is improved by growth hormone (GH) during ovarian stimulation. Additionally, patients with diabetes experience impaired insulin resistance and compromised glucose tolerance, which further exacerbate their condition. Due to these side effects, in this study, the duration of GH treatment was compared in IVF/ICSI cycles among poor ovarian responders. Methods: In this study, POSEIDON criteria were used to choose patients. Subcutaneous administration of gonadotropin-releasing hormone (GnRH) antagonist was done beginning on the sixth day of the cycle and continuing through the day of human chorionic gonadotropin (hCG) injection. In one group, GH was administered 4 units/day from the 2nd day of the cycle until hCG injection, and in another group, the first dose was administered on the 6th day of the cycle. Following the administration of hCG, which lasted from 24 to 36 hr, oocytes were retrieved with the support of B-mode sonography. Results: In our analysis, no significant differences were observed between the two groups in terms of the number of retrieved oocytes, metaphase II oocytes, and quality of grade A and B embryos. The results show that the treatment or conditions did not have a significant impact on the outcomes among the studied groups. Conclusion: Our findings indicate that a shorter duration of GH administration can yield similar outcomes compared to a longer duration in IVF/ICSI cycles involving poor ovarian responders. This result holds the potential for a more cost-effective and patient-friendly approach in managing assisted reproductive technology procedures. It may lead to reduced side effects and improved adherence to medication regimens in patients.

Natural cycle versus artificial cycle in frozen-thawed embryo transfer: A randomized prospective trial.

OBJECTIVE: To investigate whether there was a difference in pregnancy outcomes between modified natural cycle frozen-thawed embryo transfer (NC-FET) cycles and artificial cycles (AC)-FET in women who all had regular menstrual cycles. MATERIALS AND METHODS: One hundred seventy patients who met the inclusion criteria and had at least two cryopreserved embryos were included in a prospective randomized controlled trial. Eighty-five patients were randomized based on Bernoulli distribution into the following two groups: 1) Modified NC-FET using human chorionic gonadotropin for ovulation induction and 2) AC-FET, in which endometrial timing was programmed with estrogen and progesterone. The main studied outcome measure was the clinical pregnancy rate per cycle. RESULTS: No significant differences were found between the two groups with regard to the chemical, clinical, and ongoing pregnancy rates (48.2% vs 45.9%, p>0.05; 38.9% vs 35.3%, p>0.05; and 37.6% vs 34.1%, p>0.05, respectively), as well as the live birth or miscarriage rates per cycle (35.3% vs 31.8%, p>0.05; and 1.2% vs 1.2%, p>0.05, respectively). CONCLUSION: These findings suggest that although both FET protocols are equally effective in terms of pregnancy outcomes in women with regular menstrual cycles, NC-FET is more favorable because it requires no medication, has no adverse events, and has a significant cost reduction.

Comparison of Morphine Suppository and Diclofenac Suppository for Pain Management After Elective Caesarean Section.

This study investigated efficacy and side effects of Morphine suppository for pain management after the first elective caesarean delivery in comparison to Diclofenac suppository. One hundred women aged 18-40 with term pregnancies undergoing elective caesarean section for the first time participated in this prospective project. Exclusion criteria included drug sensitivity, fetal malformations or defects, and complications during the cesarean operation. After same spinal anesthesia and same surgical techniques and in the recovery room patients consecutively received 100 mg diclofenac suppository or 10 mg morphine suppository. The pain severity was rated by "Numerical Rating Scale." There was not the difference between two groups in terms of basal information. Pain score was significantly different between two groups in the first 12 hours (5.66 ±1.36 in morphine group and 3.63±0.96 in diclofenac group) but not in the second 12 hour period. Considering pain scores every two hours in first 12 hours and every 4 hours in second 12 hours, morphine group had higher scores in comparison to diclofenac group. Also, the morphine group required pethidine injection sooner than the other group. The time giving first pethidine injection was 3.28±2.16 hours after operation in morphine group and 5.24±4.07 hours after operation (P<0.05). This study demonstrated that diclofenac suppository in comparison to morphine suppository decreased subjective pain scores in the first twenty-four hours after elective caesarean section which reached statistical significance in the first twelve hours. Although in diclofenac group, pethidine injection was prescribed significantly later.

The effect of progesterone supplementation on pregnancy rates in controlled ovarian stimulation and intrauterine insemination cycles: a randomized prospective trial.

OBJECTIVE: To evaluate the effect of vaginal progesterone as luteal phase support on pregnancy rates in controlled ovarian stimulation and intrauterine insemination cycles in couples with unexplained or mild male factor infertility. STUDY DESIGN: 290 Patients who met the inclusion criteria were included in a prospective randomized controlled trial. All patients underwent controlled ovarian stimulation and intrauterine insemination: 148 patients were randomized to start with a supported cycle and 142 patients with an unsupported cycle. In supported cycles, patients received vaginal progesterone once daily from the day after insemination until 12 weeks of pregnancy or, in non-pregnant women, for 14 days. No progesterone was given during unsupported cycles. The main outcome measures were clinical pregnancy rates per cycle. RESULTS: In total, 148 cycles with luteal phase support and 142 cycles without luteal phase support were performed. The clinical pregnancy rates per cycle were higher for cycles with luteal phase support than for the unsupported cycles (24.3% vs. 14.1% respectively, p=0.027). CONCLUSION: The use of vaginal suppositories as luteal phase support significantly improved clinical pregnancy rates in controlled ovarian stimulation and intrauterine insemination in patients with unexplained or mild male factor infertility.

Secondary amenorrhea with low serum luteinizing hormone and follicle-stimulating hormone caused by an inhibin A- and inhibin B-producing granulosa cell tumor.

OBJECTIVE: Here, we report a case of secondary amenorrhea with low serum luteinizing hormone and follicle-stimulating hormone levels due to an inhibin A- and inhibin B-producing granulosa cell tumor of the ovary. CASE REPORT: A woman aged 26 with infertility, secondary amenorrhea and low levels of gonadotropin was referred to us as a case of hypothalamic amenorrhea. There was a mass measuring 56 x 41 mm in her right adnexa. We were suspicious of malignancy and checked the tumor marker levels. Laboratory findings showed high levels of inhibin A and B. She underwent an exploratory laparotomy. Microscopic examination revealed an adult granulosa cell tumor. Eighteen days after excision, she had spontaneous menstruation with normal levels of follicle-stimulating hormone and luteinizing hormone. CONCLUSION: A granulosa cell tumor secretes inhibin A and B, which suppress follicle-stimulating hormone and luteinizing hormone release through a central mechanism. This leads to amenorrhea, which can be misdiagnosed as hypothalamic amenorrhea. Inhibin producing ovarian tumors must be considered in the assessment of patients with apparent hypothalamic amenorrhea.