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.

Beneficial effects of intraovarian injection of platelet-rich plasma in women with poor ovarian response.

OBJECTIVE: Infertility can result from a diminished ovarian reserve, but a potential remedy exists in the form of platelet-rich plasma (PRP) administration. This treatment involves both biological factors and tissue trauma mechanisms, which stimulate folliculogenesis, making it a promising and effective strategy. We assessed the impact of direct PRP injections into the ovaries on the fertility outcomes of women classified as poor responders. METHODS: A quasi-experimental study was conducted from April 2021 to December 2022, focusing on patients classified as POSEIDON grade 3 or 4. PRP injections were administered into both ovaries. After 3 months, data were collected on anti-Müllerian hormone (AMH) level, follicle-stimulating hormone (FSH) level, and the numbers of oocytes, mature oocytes, and good-quality embryos following ovarian stimulation. We then compared the data from before and after PRP injection. RESULTS: This study included 50 women, with a mean of 39 years (interquartile range [IQR], 35 to 43) and 4 years (IQR, 2 to 6) for age and infertility duration, respectively. FSH levels decreased after treatment, while AMH levels and the numbers of oocytes, metaphase II oocytes, and high-quality embryos increased. However, only the increase in high-quality embryos was significant. The pregnancy and spontaneous pregnancy rates were 20% and 14%, respectively. Notably, women with secondary infertility exhibited a significantly higher pregnancy rate than those with primary infertility. CONCLUSION: Ample evidence suggests that PRP can enhance ovarian function. However, further studies are needed to identify the appropriate candidates for this procedure, establish the optimal PRP preparation method, and standardize the procedure for its adjuvant use in assisted reproductive technology cycles.

Astaxanthin ameliorates inflammation, oxidative stress, and reproductive outcomes in endometriosis patients undergoing assisted reproduction: A randomized, triple-blind placebo-controlled clinical trial.

Purpose: In a randomized, triple-blind, placebo-controlled clinical trial (RCT) including 50 infertile women with endometriosis candidate for assisted reproductive techniques (ART), we studied the effect of Astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and early pregnancy outcomes. Methods: Before and after 12 weeks of AST treatment (6 mg per day), blood serum and follicular fluid (FF) samples were collected from 50 infertile women with endometriosis stage III/IV undergoing ART. Pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and OS markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], and total antioxidant capacity [TAC]) were measured in the serum and FF. ART outcomes were also compared between the groups. Results: Increased serum levels of TAC (398.661 ± 57.686 vs. 364.746 ± 51.569; P = 0.004) and SOD (13.458 ± 7.276 vs. 9.040 ± 5.155; P = 0.010) were observed after AST therapy in the treatment group. Furthermore, serum MDA (14.619 ± 2.505 vs. 15.939 ± 1.512; P = 0.031) decreased significantly following antioxidant treatment. In addition, significantly lower serum levels of IL-1ß (4.515 ± 0.907 vs. 6.8760 ± 0.8478; P = 0.000), IL-6 (5.516 ± 0.646 vs. 5.0543 ± 0.709; P = 0.024) and TNF-α (2.520 ± 0.525 vs. 2.968 ± 0.548; P = 0.038) were observed after AST treatment. In addition, AST supplementation led to an improved number of oocytes retrieved (14.60 ± 7.79 vs. 9.84 ± 6.44; P = 0.043), number of mature (MII) oocytes (10.48 ± 6.665 vs. 6.72 ± 4.3; P = 0.041), and high-quality embryos (4.52 ± 2.41 vs. 2.72 ± 2.40; P = 0.024). Conclusion: AST pretreatment can modulate inflammation and OS in endometriosis-induced infertile patients. ART outcomes also improved after 12 weeks of AST therapy. Our results suggest that AST can be a potential therapeutic target for infertile patients with endometriosis undergoing ART.

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.

Randomized controlled trial of astaxanthin impacts on antioxidant status and assisted reproductive technology outcomes in women with polycystic ovarian syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, is typically accompanied by a defective oxidative defense system. Here, we investigated the effect of astaxanthin (AST) as a powerful antioxidant on the oxidative stress (OS) response and assisted reproductive technology (ART) outcomes in PCOS patients. METHODS: In this double-blind, randomized, placebo-controlled trial, PCOS patients were randomly assigned into two groups. The intervention group received 8 mg AST, and the control group received the placebo daily for 40 days. The primary outcomes were the serum and follicular fluid (FF) levels of the OS biomarkers and the expression levels of the specific genes and proteins in the oxidative stress response pathway. The secondary outcomes were considered ART outcomes. RESULTS: According to our findings, a 40-day course of AST supplementation led to significantly higher levels of serum CAT and TAC in the AST group compared to the placebo group. However, there were no significant intergroup differences in the serum MDA and SOD levels, as well as the FF levels of OS markers. The expression of Nrf2, HO-1, and NQ-1 was significantly increased in the granulosa cells (GCs) of the AST group. Moreover, the MII oocyte and high-quality embryo rate were significantly increased in the AST group compared to the placebo group. We found no significant intergroup difference in the chemical and clinical pregnancy rates. CONCLUSION: AST treatment has been shown to increase both serum TAC levels and activation of the Nrf2 axis in PCOS patients' GCs. TRIAL REGISTRATION: ClincialTrials.gov Identifier: NCT03991286.

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 efficacy of gonadotropin-releasing hormone (GNRH) agonist before frozen embryo transfer in improving pregnancy outcome and decreasing miscarriage rate in hyperandrogenic polycystic ovary syndrome women: a randomized clinical trial.

BACKGROUND: The hyper androgenic status is a major complication of polycystic ovarian syndrome (PCOS) that deteriorates endometrial function and increases miscarriage rate. This study was conducted to investigate the efficacy of GnRH agonist before frozen-thawed embryo transfer in improving pregnancy outcome in infertile women with PCOS. METHODS: This single-blind, randomized controlled trial was performed at Dr Shariati hospital and Omid Fertility Clinic in Tehran, Iran. In the study were included 178 PCOS women. Patients were then divided into two groups of control and intervention. All women received the standard treatment for the preparation of the endometrial using estradiol valerate at dose of 6-8 mg/day. The intervention group also received diphereline, as GnRH agonist, at two doses, 8 weeks before starting the endometrial preparation. RESULTS: Chemical pregnancy in intervention group was 47.7% compared to 35.6% in the control group, revealing no significant difference between two groups. No statistically significant difference was observed between two groups concerning clinical pregnancy rate (43.2% vs. 27.3%). However, rate of ongoing pregnancy was 42.0% in intervention group but 18.0% in the control group, suggesting a significant difference (P=0.001). The rate of miscarriage in the intervention group was 2.6% and in the control group was 33.3%, which was significantly lower (P=0.001). CONCLUSIONS: It can be concluded that endometrial preparation using GnRH improves ongoing pregnancy and decreases miscarriage rate. It seems that reduction of androgen level in PCOS patients affects the endometrium and improves the receptivity and implantation of the embryo, resulting in better pregnancy outcomes by reducing the miscarriage rate.

Cervical cancer screening and Pap test non-adherence risk factors in systemic sclerosis patients.

Systemic sclerosis is a rare autoimmune disorder that potentially affects nearly every organ of the body. Malignancies are one of the most common non-systemic sclerosis related cause of mortality. There are controversial findings regarding the cervical cancer rate among these patients, but prolonged immunosuppressive medication makes them more susceptible to cervical cancer. In the present study, we have aimed to investigate the cervical cancer screening result and the Pap test non-adherence risk factors among systemic sclerosis patients. This cross-sectional study was conducted on 100 systemic sclerosis patients. The clinicodemographic variables in addition to cervical cancer risk factors were obtained from the patients. Pap test performed using the liquid-based method. The non-adherence risk factors were determined by univariate and multivariate logistic regression analysis. Benign inflammatory and atrophic changes were reported in 26 and 5%, respectively. None of the cases had abnormal cytological finding. Twenty-two percent of the participants were a routine Pap test performer. According to the multivariate model, higher age was associated with Pap test non-adherence [odds ratio (95% confidence interval): 1.058 (1.010-1.108) and P-value: 0.018]. In the present study, we have shown that compliance with Pap test performing is extremely low among Iranian systemic sclerosis patients. In addition, we have demonstrated that older age is a risk factor for non-adherence. These findings highlighted the crucial role of the physicians in motivating the patients toward cancer screening.

Growth Hormone (GH) Improvement of Ovarian Responses and Pregnancy Outcome in Poor Ovarian Responders: A Randomized Study.

Recent evidence has emphasized growth hormone benefits in increasing the ovarian response and improving the pregnancy rate in poor responders (POR), caused by aging, ovarian surgery, chemotherapy and other reasons, undergoing IVF/ICSI. The most important factor in the treatment of POR patients is the quality and quantity of oocytes following ovarian stimulation; thus, efforts should be made to provide opportunities for young patients to improve their fertility and ovarian responses. The use of GH in these patients may offer a promising aid to successful fertility.In the present single-blinded clinical trial, POR patients were randomly assigned to receive one of three regimens: (A) Gonadotropin, a GnRH antagonist and GH from the eighth day of the cycle for about 5 days (n = 34); (B) Gonadotropin, a GnRH antagonist and GH from the third day of the previous cycle for about 20 days (n = 32); and (C) Gonadotropin, a GnRH antagonist, and a placebo from the eight day of the cycle for about 5 days (n = 26). Oocyte quality and pregnancy rates were compared across the three groups. A significantly lower number of collected oocytes, MII oocytes, fertilized oocytes, transferred embryos, and clinical pregnancy rate in the placebo group was noted as compared to the two experimental groups receiving GH. Live clinical pregnancies in B group were significantly greater than in the other groups. Our results together indicate that GH may play an important role in recruitment of dominant follicles and enhance follicular survival and the cell proliferation leading to high- quality embryos. Accordingly, administration of GH can considerably elevate the ovarian response in patients with POR planned to undergo IVF.

Autologous Platelet-Released Growth Factor and Sexual Dysfunction Amendment: A Pilot Clinical Trial of Successful Improvement Sexual Dysfunction after Pelvic Irradiation

Sexual dysfunction (SDF) is a common sequel to cancer treatment which affects the quality of life in women treated with pelvic radiotherapy. The aim of this study was to evaluate the safety, symptom resolution and objective improvement the injection of autologous platelet released growth factor (APRGF) for treatment of SDF in cited patients. This prospective pilot study enrolled 10 cancer-free patients with SDF who underwent pelvic radiotherapy at least 5 years ago, randomly. Each patient was received 1-2 cc APRGF within four weeks and all patients were re-evaluated at eight weeks and six months. CD34 immuno histochemistry and Masson's trichrome staining were performed on vaginal biopsy section for angiogenesis and fibrosis assay respectively. Sexual satisfaction after the injection of APRFG was clinically difference and the entire patient had sexual satisfaction. In the patient's follow-up, none of them needs to repeat the treatment. Our results declared that APRGF injection was effective and symptoms were disappeared in the entire patients. Significant objective improvements in vaginal diameter (mean before injection, 6.5 cm vs 7.1 cm after injection) (p-value = 0.001) and vaginal flexibility (mean before treatment, 0.72 cm vs 1.85 cm after injection) (P-value = 0.026) were observed. Characteristics of discharge before the injection in 60% of patients were included dry vagina and 40% had mild discharge but after injection 40% of patients had moderate and also 60% had mild and sufficient discharge (P-value= 0.190). Overally, our patients reported better sexual function and showed better vaginal function indexes, after APRFG injection.

Effects of letrozole and clomiphene citrate on Wnt signaling pathway in endometrium of polycystic ovarian syndrome and healthy women†.

Polycystic ovary syndrome (PCOS) is an endocrine disorder in women of reproductive age. In addition to anovulation, endometrial dysfunction can reduce fertility in PCOS. The cyclical changes of endometrium are controlled by estrogen and progesterone via modulating the Wnt/B-catenin pathway. Clomiphene citrate (CC) and letrozole are used to induce ovulation; unlike letrozole, there is a discrepancy between ovulation and pregnancy rates in CC-treated cycles. Because of the anti-estrogenic effects of CC on endometrium, we compared the expression of the key molecules of the Wnt/B-catenin pathway in the endometrium of women taking CC and letrozole. This study included PCOS and healthy women divided into the groups stimulated with letrozole (5 mg) or CC (100 mg) as well as NO-treatment groups. The endometrial thickness and hormonal profile were measured on day 12 of the menses. Using real-time polymerase chain reaction and western blot, we evaluated mRNA and protein expression of B-catenin, glycogen synthase kinase 3 beta (GSK3B), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), and estrogen receptor 1 (ESR1) in the endometrial samples. Significantly, the mean serum estrogen and progesterone were lower and higher, respectively, in letrozole than CC groups. The endometrial thickness was significantly reduced in CC. The proteins expression of active B-catenin, inactive GSK3B, and ESR1 were significantly decreased in CC-treated groups. The mRNA and protein assessment of DKK1 showed significantly higher expression in CC. Our results indicate that letrozole can provide an acceptable activation of the Wnt/B-catenin pathway, resulting in adequate proliferation of endometrium in the women receiving letrozole compared to CC.

The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a, and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/ß-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100 mg CC or 5 mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.

GnRH agonist trigger versus hCG trigger in GnRH antagonist in IVF/ICSI cycles: A review article.

Routinely, a bolus of 5.000-10.000 IU human chorionic gonadotropin (hCG) is used for the final follicular maturation and ovulation as a standard method. HCG has the same effect of luteinizing hormone (LH) with long half-life. It has the long lutheotrophic effect which increases the risk of ovarian hyper stimulation syndrome (OHSS). Recently, gonadotropin-releasing hormone agonist (GnRH-a) trigger has been used for the induction of final follicular maturation and ovulation with the aim of reducing the OHSS risk. Several studies have shown that the releases of endogenous follicular stimulating hormone (FSH) and LH after administration of GnRH agonist in in vitro fertilization (IVF) cycles are able to precede the final follicular maturation leading to removal of fertile oocyte with normal development of the embryo and ultimately pregnancy. But based on the results of some studies, using GnRH-a trigger leads to defect luteal-phase resulting to reduce the implantation and clinical pregnancy rates and also increase abortion in fresh embryo transfer cycles compared to routine IVF cycle with hCG triggering . Also, in recent years, studies have continued to modify the luteal phase support, so that the fresh embryo transfer is possible too. In this review, we examined the benefits, problems, and also ways to reform GnRH agonist triggering complications.