Effect of intraovarian platelet-rich plasma injection on IVF outcomes in women with poor ovarian response: the PROVA randomized controlled trial.

STUDY QUESTION: Does intraovarian platelet-rich plasma (PRP) injection increase the number of mature oocytes obtained after controlled ovarian stimulation (COS) in young women with poor ovarian response (POR) undergoing IVF? SUMMARY ANSWER: Intraovarian PRP injection procedure does not improve mature oocyte yield after COS in women less than 38 years old with an established IVF history of POR. WHAT IS KNOWN ALREADY: POR is frequently encountered among the infertile population and the number of women seeking infertility treatment related to POR is increasing. Effective treatment options for this patient population to conceive with autologous oocytes are lacking. Case series and cohort studies suggest that intraovarian PRP injection may improve follicular recruitment in women with premature ovarian insufficiency (POI) and POR, yet robust randomized studies have not been performed to date to determine the clinical utility of this intervention. STUDY DESIGN, SIZE, DURATION: This was a multi-center randomized controlled trial (RCT) conducted at university-affiliated reproductive centers in the USA and Turkey, between January 2020 and November 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients who met inclusion criteria (<38 years old, two or more prior cycles with <3 oocytes retrieved; and without single gene disorders, prior ovarian surgery, endometriomas, BMI >35 kg/m2, or severe male factor infertility) were randomized to either the PRP or control group. Patients in both groups subsequently underwent COS, oocyte retrieval, ICSI, preimplantation genetic testing for aneuploidy (PGT-A), and single euploid embryo transfer. Number of metaphase II (MII) oocytes obtained was the primary outcome. Secondary outcomes included ovarian reserve tests (antral follicle count [AFC] and anti-Müllerian hormone [AMH]), blastocyst and euploid blastocyst yields, and sustained implantation. The study was powered to detect a difference of one mature oocyte obtained at oocyte retrieval. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 83 patients met inclusion criteria and were randomized to receive autologous intraovarian PRP injection (n = 41) or to no intervention (n = 42). No significant differences were observed in number of MII oocytes retrieved per cycle (2.8 ± 2.4 vs 3.1 ± 3.3 in PRP vs control, respectively; P = 0.9), blastocysts (1.0 ± 1.3 vs 1.3 ± 2.1, P = 0.8), or euploid blastocysts (0.8 ± 1.1 vs 0.9 ± 1.6; P = 0.5). Similarly, no differences were observed in the likelihood of obtaining at least one euploid blastocyst (45% vs 37%, P = 0.4; relative risk [RR], 95% CI = 0.9, 0.6-1.2) or the rate of sustained implantation (31% vs 29%, P = 0.9; RR 1.0, 0.7-1.3). Posttreatment AFC (7.9 ± 4.5 vs 6.8 ± 4.8, P = 0.3) and AMH (0.99 ± 0.98 vs 0.7 ± 0.6, P = 0.2) were also not different between the groups. LIMITATIONS, REASONS FOR CAUTION: Results from this RCT may not be generalizable to other PRP preparations owing to heterogeneity and lack of standardization. The control groups did not undergo a sham ovarian injection, which would have been relevant had the results shown benefit of PRP injection. Only patients with POR were included in this study, and these results may not be generalizable to more severe diminution of ovarian reserve, as seen with POI. WIDER IMPLICATIONS OF THE FINDINGS: The intraovarian PRP injection procedure does not improve mature oocyte yield or other parameters of IVF outcome in women less than 38 years old with an established IVF history of POR. The results from this study do not support the use of intraovarian PRP injection in this population. STUDY FUNDING/COMPETING INTEREST(S): Departmental funds were used and no external funding was requested for this study. ES is a consultant for and receives grant funding from the Foundation for Embryonic Competence. All other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov Registry Identifier: NCT04163640. TRIAL REGISTRATION DATE: 15 November 2019. DATE OF FIRST PATIENT'S ENROLMENT: 24 February 2020.

Effects of preconceptional vitamin D levels on in vitro fertilization outcomes in infertile patients with polycystic ovary syndrome: A retrospective cohort study.

BACKGROUND: Vitamin D plays various roles in different stages of reproduction, and abnormalities in its levels are associated with diseases such as polycystic ovary syndrome (PCOS). This study aimed to determine the relationship between initial vitamin D levels and in vitro fertilization (IVF) outcomes in PCOS patients. METHODS: This retrospective cohort study included 1174 PCOS patients who consulted the Acibadem Maslak Hospital IVF Clinic between January 2015 and March 2021. We investigated the effect of preconceptional vitamin D levels on IVF outcomes using data analysis with SigmaPlot 14.5. RESULTS: We found a significant positive correlation between preconceptional vitamin D levels and positive clinical pregnancy rates (p < 0.001) as well as increased endometrial thickness (EMT) on human chorionic gonadotropin (hCG) day (p < 0.001, r = 0.262). The optimal vitamin D cut-off value for predicting positive hCG test results was identified as 13.24 ng/mL, as determined by receiver operating characteristic curve analysis (sensitivity = 0.839, specificity = 0.677). No association was observed with other IVF outcome parameters, miscarriage rates, or clinical pregnancy rates based on EMT. CONCLUSIONS: The study suggests that PCOS patients with vitamin D levels above 13.24 ng/mL are more likely to achieve positive hCG results after IVF. These findings highlight the potential importance of vitamin D supplementation in improving pregnancy outcomes for PCOS patients. Additionally, increased EMT on hCG day may explain the higher clinical pregnancy rates associated with elevated vitamin D levels.

The effect of intratesticular autologous platelet-rich plasma injection on sperm retrieval rates and in vitro fertilization outcomes in couples with non-obstructive azoospermia.

AIM: To assess the efficacy of intratesticular injection of autologous platelet-rich plasma (PRP) in men with non-obstructive azoospermia (NOA) and a history of failed microdissection-testicular sperm extraction (mTESE) procedures. METHODS: A prospective case series of a cohort study was conducted involving couples diagnosed with NOA. Patients with at least one failed mTESE procedure were included. Intratesticular PRP injection was performed using a standardized protocol. Follow-up assessments included sperm analysis, hormonal evaluation, and in vitro fertilization (IVF) outcomes. RESULTS: Data from 177 men with NOA were analyzed, with 135 patients meeting eligibility criteria. PRP treatment resulted in positive sperm retrieval rates of 27.5% in patients with one prior failed mTESE procedure and 16.4% in patients with two or more failed attempts. IVF outcomes showed fertilization rates of 86.4% and 100.0% in respective groups, with pregnancy rates of 36.8% and 22.2% per embryo transfer. Histopathological examination post-mTESE revealed varied patterns, including Sertoli cell-only syndrome and maturation arrest. CONCLUSIONS: Intratesticular PRP injection shows promise as a potential therapeutic approach for NOA patients with prior failed mTESE procedures, demonstrating improved sperm retrieval rates and favorable IVF outcomes. Further randomized controlled trials are warranted to validate these findings and refine the technique's efficacy in male infertility management to answer the question of whether PRP could significantly improve the second attempt retrieval rate.

Treatment options for endometrial hypoproliferation.

PURPOSE OF REVIEW: Endometrial hypoproliferation refers to the failure of the endometrium to reach optimal thickness during fresh or frozen embryo transfer cycles in women undergoing infertility treatment with in-vitro fertilization (IVF). This review discusses the treatment options for endometrial hypoproliferation. RECENT FINDINGS: Apart from factors related to the embryo quality, ultrasonographic findings associated with the endometrium, such as endometrial thickness, endometrial pattern and subendometrial blood flow, are considered key factors associated with the outcome of assisted reproductive treatment. To date, a consensus has not been reached regarding the definition of thin endometrium, while thresholds of 6, 7 or 8 mm have been used in the literature. Strategies to increase endometrial thickness can be reviewed in three groups: endocrine approaches, vitamins & supplements, and new experimental therapeutic interventions. Some of the recently introduced experimental therapeutic interventions such as platelet-rich plasma injection, stem cell treatment and tissue bioengineering are exciting potential therapies that need to be further studied. SUMMARY: Despite a large number of publications on the topic, diagnosing and treating endometrial hypoproliferation remains a challenge. Well designed studies are needed to establish a widely accepted endometrial thickness cut-off value below which endometrial hypoproliferation is diagnosed and to generate meaningful data that would allow an evidence-based discussion of available therapeutic options with patients.

Thyroid hormones and ovarian reserve: a comprehensive study of women seeking infertility care.

BACKGROUND: Ovarian reserve is the number of oocytes remaining in the ovary and is one of the most important aspects of a woman's reproductive potential. Research on the association between thyroid dysfunction and ovarian reserve has yielded controversial results. In our study, we aimed to investigate the relationship between thyroid-stimulating hormone (TSH) levels and ovarian reserve markers. METHODS: From 1443 women seeking infertility care, the data of 1396 women aged between 20-45 years old who had a body mass index between 18-30 kg/m2 were recruited for this retrospective study. The anti-Müllerian hormone (AMH) and TSH relationship was analyzed with generalized linear and polynomial regression. RESULTS: Median age, follicle-stimulating hormone (FSH), AMH, and TSH levels were 36.79 years, 9.55 IU/L, 3.57 pmol/L, and 1.80 mIU/L, respectively. Differences between TSH groups were statistically significant in terms of AMH level, antral follicle count (AFC), and age (p = 0.007 and p = 0.038, respectively). A generalized linear regression model could not explain age-matched TSH levels concerning AMH levels (p > 0.05). TSH levels were utilized in polynomial regression models of AMH, and the 2nd degree was found to have the best fit. The inflection point of the model was 2.88 mIU/L. CONCLUSIONS: Our study shows a correlation between TSH and AMH values in a population of infertile women. Our results are as follows: a TSH value of 2.88 mIU/L yields the highest AMH result. It was also found that AMH and AFC were positively correlated, while AMH and FSH were negatively correlated.

Determining diagnostic criteria and cause of recurrent implantation failure.

PURPOSE OF REVIEW: Recurrent implantation failure (RIF) refers to the absence of implantation after repeated transfer of good embryos into a normal uterus. This review discusses the diagnostic criteria and cause of RIF. RECENT FINDINGS: Regardless of the advancements in IVF practice, RIF is still a challenge that has to be solved. Exact definition of RIF is lacking today. For the initial evaluation, a rigorous algorithmic evaluation should be compromised with an individualized principle. Factors that might affect the number and quality of the oocyte and sperm cells should be investigated in order to obtain a good-quality embryo. Embryo assessment should be performed under ideal laboratory circumstances. The uterine environment should be carefully evaluated and the embryo should be transferred into the uterus at the most receptive time. Some of the newly introduced diseases and empirical treatment strategies, such as chronic endometritis, vaginal microbiota, immunologic profile and immunomodulator treatments, can be discussed with the couple under the light of adequate evidence-based information. SUMMARY: New diagnostic and treatment modalities are needed to be introduced, which would be safe, efficient and efficacious after well-designed randomized controlled trials.

Might retrigger with human chorionic gonadotropin be a solution for empty follicle syndrome after gonadotropin releasing hormone agonist trigger?

Objective: This study aimed to determine whether the use of human chorionic gonadotropin (hCG) as a trigger could offer a potential solution for addressing empty follicle syndrome following the administration of a trigger for gonadotropin-releasing hormone agonist. Materials and Methods: A retrospective cohort analysis was conducted using data extracted from the hospital database pertaining to 415 patients who underwent in vitro fertilization (IVF) with an antagonist protocol triggered by a gonadotropin-releasing hormone (GnRH) agonist between December 2019 and January 2023 at the Acibadem Maslak Hospital Assisted Reproductive Technologies Unit. All cases that failed to obtain oocytes and required rescue were analyzed. Results: This study analyzed 415 women who underwent IVF using GnRH agonist-triggered antagonist protocols. Among them, 6 (1.4%) had empty folicle syndrome (EFS). Patients with EFS had lower luteinizing hormone levels and fewer oocytes, embryos, and blastocysts, resulting in lower oocyte utilization rate. However, pregnancy rates were similar, with no biochemical or ectopic pregnancies observed in the EFS group. Conclusion: Use of an hCG retrigger in hyperresponders with no oocytes after GnRHa trigger may prevent cycle cancelation. Although the rates of egg utilization may decrease, oocyte maturity remains comparable. Frozen embryo transfer following hCG retrigger administration yields similar positive pregnancy test results and live birth rates.

Effects of Non-Cavity-Distorting Intramural Fibroids on IVF Outcomes in Patients with Recurrent IVF Failure: Does Myomectomy Change IVF Outcomes ?

Background: Uterine fibroids are the most common benign smooth muscle tumors of the uterus. However, there is no consensus on whether myomectomy improves IVF success in women with non-cavity-distorting intramural fibroids. The aim of this study was to compare the IVF and pregnancy outcomes of women who had non-cavity-distorting intramural fibroids and underwent myomectomy vs women who had intramural fibroids, but did not undergo myomectomy. Methods: A retrospective cohort study at Acibadem Maslak Hospital, IVF Center, between 2019 and 2020. Data of 128 women aged between 25 and 43 years who have at least 2 intramural non-cavity-distorting fibroids of 2-6 cm in size were used. All patients had at least two IVF failure. The intervention group comprised women who decided to proceed to myomectomy before IVF (Group 1, n = 56). The control group was established women with intramural fibroids who reject myomectomy (Group 2, n = 71). Results: In regard to IVF result parameters and perinatal outcomes, there was no statistically significant difference between the two groups. Between study groups, there were no statistically significant differences in the perinatal outcomes. Myomectomy surgery did not increase miscarriage and biochemical pregnancy rate (odds ratio (OR) 0.9; 95% confidence interval (CI) 2.8-3.7). Conclusion: Myomectomy does not impact on pregnancy or live birth rates substantially, according to the results of this study.

Does dual trigger improve euploidy rate in normoresponder? A cross-sectional study.

Background: With the introduction of the dual triggering-gonadotropin-releasing hormone (GnRH) analog and recombinant human chorionic gonadotropin (hCG) combination, women with a history of low mature oocyte proportion and empty follicle syndrome were shown to benefit from the dual trigger. Objective: To investigate whether dual triggering of oocyte maturation with a GnRH agonist (GnRHa) combined with hCG can affect the euploidy rate and improve in vitro fertilization outcomes for normoresponder women. Materials and Methods: In this cross-sectional study, 494 women who underwent controlled ovarian stimulation with hCG (n = 274) or dual triggering (hCG+GnRHa, n = 220) at Acibadem Maslak hospital, Assisted Reproductive Unit, from January 2019-2022 were enrolled in this study. Preimplantation genetic testing for aneuploidy was performed on all participants. Results: Both groups had similar baseline and clinical characteristics. Of the 881 embryos biopsied, 312 (35.4%) were reported as euploid in the hCG trigger group; in the dual trigger group, 186 (29.8%) of 623 screening embryos were reported as euploid. The hCG group had a higher euploidy rate per biopsied embryo, although the difference was not statistically significant (31.4 ± 26.5 vs. 26.5 ± 33.3, p > 0.05). Conclusion: In normoresponders, adding GnRHa for final follicular maturation to hCG did not improve the euploidy rate.

Distress response in granulosa cells of women affected by PCOS with or without insulin resistance.

PURPOSE: In this study, we investigated whether metabolic dysfunction in women with Polycystic ovarian syndrome (PCOS) induces granulosa cell (GC) stress and activates in the endoplamatic reticulum and the mitochondria (UPRer and UPRmt, respectively). METHODS: Women who were diagnosed with PCOS (based on the Rotterdam criteria), were divided into two groups, PCOS with insulin resistance (PCOS-IR; n = 20) and PCOS with no insulin resistance (PCOS-nIR; n = 20), and compared to healthy oocyte donors (CONT; n = 20). Insulin resistance (IR) was assessed on the results of homeostasis model assessment (HOMA) that determines IR using the concentration of fasting plasma glucose and fasting insuline. Expression of UPRer genes (i.e., IRE1, ATF4, ATF6, XBP1, BIP, and CHOP), and UPRmt genes (i.e., HSP60, HSP10, CLPP, and HSP40) was assessed in cumulus GCs by qRT-PCR. RESULTS: We found that several genes involved in UPRer and UPRmt were overexpressed in the GCs of PCOS-IR and PCOS-nIR compared to CONT. IRE1, ATF4 and XBP1, that are activated by ER stress, were significantly overexpressed in PCOS-IR compared to CONT. BIP and CHOP were overexpressed in PCOS groups compared to CONT. HSP10 and HSP40 were upregulated in PCOS-IR and PCOS-nIR groups compared to the CONT. HSP60 and CLPP showed no statistical different expression in PCOS-IR and PCOS-nIR compared to CONT group. CONCLUSION: Our findings suggest that the GCs of women with PCOS (with or without IR) are metabolically distressed and upregulate UPRer and UPRmt genes. Our study contributes to the understanding of the molecular mechanisms underlying the pathological changes that occur in the follicular microenvironment of women with PCOS.

Germline cells in ovarian surface epithelium of mammalians: a promising notion.

It is a long held doctrine in reproductive biology that women are born with a finite number of oocytes and there is no oogenesis during the postnatal period. However, recent evidence challenges this by showing the presence of germ line stem cells in the human ovarian surface epithelium (OSE), which can serve as a source of germ cells, and differentiate into oocyte like structures. Postnatal renewal of oocytes may have enormous therapeutic potential especially in women facing the risk of premature ovarian failure idiopathically or iatrogenically after exposure to gonadotoxic chemotherapy and radiation for cancer therapy.This article reviews current knowledge on germ line stem cells in human OSE.

Management of endometrial polyps diagnosed before or during ICSI cycles.

This retrospective study aimed to shed light on the management options of endometrial polyps diagnosed before or during intracytoplasmic sperm injection (ICSI) treatment. The study included all fresh ICSI cycles performed in the Anatolia IVF Center between July 2005 and January 2009. Group 1 consisted of 47 patients who were diagnosed with an endometrial polyp before their ICSI cycle. All patients diagnosed with an endometrial polyp by transvaginal ultrasonography before the ICSI cycle underwent hysteroscopic polyp resection. Group 1 was compared with 47 matched control patients without endometrial polyps who underwent standard ICSI cycles (group 2). Group 3 included 128 patients diagnosed with an endometrial polyp during stimulation in their ICSI cycles. Group 3 was compared with 128 matched control patients without endometrial polyps who underwent standard ICSI cycles (group 4). Patients diagnosed with an endometrial polyp before ICSI cycles were similar to their controls with regard to clinical pregnancy (29.8% versus 38.3%) and live-birth (25.5% versus 31.9%) rates per transfer, as were patients diagnosed with an endometrial polyp during ovarian stimulation (clinical pregnancy rates 45.3% versus 46.9%; live-birth rates 40.6% versus 39.8%). In conclusion, further studies are required to identify the most appropriate management of endometrial polyps.

What should be the strategy in case of a big follicle at the start of the cycle? Shall we start the stimulation or postpone it to the next cycle?

Objective: This study facilitates decision-making when an antral follicle diameter >15 mm is detected at the beginning of the menstrual cycle in poor responder (POR) patients. Materials and Methods: Eighty-three POR patients with at least one leading follicle with a diameter of 15 to 24 mm on the 2nd-4th days of the menstrual cycle were assessed. Results: The mean age of females was 40.1±4.8 (26-45), and the mean partners' age was 42.1±7.8 (26-65). Fifty-one (61.4%) women underwent an oocyte pick-up procedure 36 h after the first ultrasonographic examination on the 2nd-4th days of the menstrual cycle. Gonadotrophin stimulation was initiated in 32 (38.6%) patients. Among women in whom oocyte retrieval was performed, an oocyte was obtained in 49 (59.75%) patients. In 13 of 49 patients (26.5%), no mature oocytes were obtained. Fertilized 2pn embryos were obtained in 18 of 33 patients (54.5%). Among the fertilized embryos, 12 were good, six were moderate, and two were of poor quality. Following the frozen embryo transfer procedure, one of the two patients experienced a clinical pregnancy. Conclusion: Patients with POR are still difficult to manage both clinically and therapeutically. Since every oocyte is valuable and important, patients should be carefully followed up. Our research will be directed by the need to rule out a physiological ovarian cyst when large antral follicles appear at the beginning of the cycle. The clinician should give them a chance.

Ovarian reserve parameters and IVF outcomes in 510 women with poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP).

The aim of the current study was to characterize ovarian reserve parameters and IVF outcomes in women with a history of poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP). Reproductive age women (N=510; age range 30-45yo) diagnosed with POR based on Poseidon criteria were included in the study. PRP treatment resulted in higher AFC, higher serum AMH, lower serum FSH, and a higher number of mature oocytes and cleavage and blastocyst stage embryos. After PRP injection, 22 women (4.3%) conceived spontaneously, 14 (2.7%) were lost to follow up, and 474 (92.9%) attempted IVF. Among women who attempted IVF, 312 (65.8%) generated embryos and underwent embryo transfer, 83 (17.5%) achieved a pregnancy, and 54 (11.4%) achieved sustained implantation/live birth (SI/LB). In total, of the 510 women with POR and mean age of 40.3, PRP resulted in improvement of ovarian reserve parameters, a pregnancy rate of 20.5% and SI/LB rate of 12.9%. Our findings suggest that PRP treatment may be considered in women with POR. For wider clinical application, its clinical efficacy will need to be demonstrated in prospective randomized clinical trials.

Comparison of diagnostic accuracy of saline infusion sonohysterography, transvaginal sonography and hysteroscopy in postmenopausal bleeding.

OBJECTIVE: To compare the diagnostic accuracy of transvaginal sonography (TVS), saline infusion sonohysterography (SIS) and hysteroscopy (HS) with respect to pathological diagnosis in the detection of uterine cavity abnormalities associated with abnormal uterine bleeding among postmenopausal women. METHODS: Being a prospective, investigator-blind trial, the present study was conducted on 137 postmenopausal women, with abnormal uterine bleeding, admitted to the Department of Obstetrics and Gynecology of Istanbul Bilim University, Florence Nightingale Hospital and Fertigyn Woman Health and IVF Center. After TVS, all patients underwent SIS using Cook Soft 500 IVF transfer catheter and HS, consecutively. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated to compare the diagnostic accuracy of TVS, SIS and HS. RESULTS: Most commonly encountered endometrial lesions were polypoid lesion (38.0%) and hyperplasia (28.4%) among our study population consisting of 137 women (mean age 61.6 ± 9.6 years) in their postmenopausal stage. Overall sensitivity rates were 70.0% for TVS, 89.6% for SIS and 92.3% for HS, while the overall specificity rates were 50.0, 77.3 and 80.7%, respectively. HS had PPV of 96.2% and NPV of 65.3%, whereas PPV was determined to be 80.9 versus 95.3% and NPV was 35.4 versus 58.3% for TVS and SIS, respectively. CONCLUSIONS: As an easy to perform, safe and well-tolerated procedure yielding high diagnostic accuracy, saline infusion SIS via this catheter seems to be superior to TVS and very close to HS. It may be used as the primary method for the detection of uterine abnormalities among postmenopausal women with abnormal uterine bleeding.

Intracytoplasmic sperm injection outcome of women over 39: an analysis of 668 cycles.

PURPOSE: To evaluate intracytoplasmic sperm injection (ICSI) outcome of women over age 39 and to determine when to discourage such couples to undergo IVF using their own oocytes. METHODS: Four hundred ninety-five consecutive women (n=668 cycles) over age 39 were evaluated by year-by-year age increments to discriminate the independent prognostic factors for the achievement of pregnancy. RESULTS: Although the ovarian hyperstimulation performance (COH) and embryological data were not too diverse, the clinical pregnancy rates per embryo transfer decreased from 26 to 13% from age 40 to 44. According to logistic regression, the female age seems to be the only variable in order to predict an ongoing pregnancy. The miscarriage rate increased with advancing female age. It was 33% at age 40 but increased to 100% by age 45. CONCLUSIONS: The performance of COH and embryological data is not discouraging among women over 39 years in ICSI cycles. However, increased miscarriages as well as decreased implantation rate are mainly responsible for the poor performance of patients with advanced female age. Irrespective of the ovarian reserve testing, ICSI may be refused at age 45 and thereafter.

Effects of hormone replacement therapy on glucose and lipid profiles and on cardiovascular risk parameters in postmenopausal women.

OBJECTIVES: The aim of this study was to evaluate the effects of hormone replacement therapy (HRT) on carbohydrate and lipid metabolisms and cardiovascular risk parameters in healthy postmenopausal women. METHODS: Forty women receiving and 38 women not receiving HRT were included and baseline and sixth month blood pressure, weight, body mass index, waist/hip ratio, blood lipid profile, inflammatory markers (homocysteine, C-reactive protein (CRP) and fibrinogen), hemoglobin A1c (HbA1c) and insulin, and oral glucose tolerance test (OGTT) results were evaluated. RESULTS: The mean age was 52.6+/-4.9 and 52.2+/-5.0 years in the HRT and Control Groups, respectively. Whereas there was no change in the Controls, the weight, waist/hip ratio, and BMI increased and diastolic blood pressure decreased in the HRT patients. LDL-c, VLDL-c and lipoprotein (a) levels were significantly higher in the HRT Group in the sixth month; however, total cholesterol and LDL-c increased in the Controls but VLDL-c and lipoprotein (a) did not. CRP and homocysteine significantly increased and fibrinogen decreased, whereas in the Control Group no significant change was detected. A significant improvement in HbA1c and OGTT was found in both the groups, whereas a significant reduction was measured only in the HRT Group. CONCLUSIONS: In response to 6 months of HRT, there was an increase in weight, BMI, and waist/hip ratio as known cardiovascular risk factors, but no significant impact on lipid profile and glucose metabolism could have been clearly demonstrated. A mixed effect profile of HRT on the state of inflammation (increase in CRP and homocysteine, decrease in fibrinogen) was observed.

Effects of intraovarian injection of autologous platelet rich plasma on ovarian reserve and IVF outcome parameters in women with primary ovarian insufficiency.

We aimed to determine whether intraovarian injection of autologous platelet rich plasma (PRP) improves response to ovarian stimulation and in vitro fertilization (IVF) outcome in women with primary ovarian insufficiency (POI). Women (N=311; age 24-40) diagnosed with POI based on ESHRE criteria underwent intraovarian PRP injection. Markers of ovarian reserve, and IVF outcome parameters were followed. PRP treatment resulted in increased antral follicle count (AFC) and serum antimullerian hormone (AMH), while serum follicle stimulating hormone (FSH) did not change significantly. After PRP injection, 23 women (7.4%) conceived spontaneously, 201 (64.8%) developed antral follicle(s) and attempted IVF, and 87 (27.8%) had no antral follicles and therefore did not receive additional treatment. Among the 201 women who attempted IVF, 82 (26.4% of total) developed embryos; 25 of these women preferred to cryopreserve embryos for transfer at a later stage, while 57 underwent embryo transfer resulting in 13 pregnancies (22.8% per transfer, 4% of total). In total, of the 311 women treated with PRP, 25 (8.0%) achieved livebirth/sustained implantation (spontaneously or after IVF), while another 25 (8.0%) cryopreserved embryos. Our findings suggest that in women with POI, intraovarian injection of autologous PRP might be considered as an alternative experimental treatment option.

ICSI outcome following conservative fertility sparing management of endometrial cancer.

Approximately 5% of cases of endometrial cancer occur in women aged 40 years or younger. In the presence of early staged endometrial cancer, fertility sparing management may be considered in selected patients. Following high dose progestin therapy and confirmation of the regression of cancer, the patient might attempt to conceive spontaneously. However, assisted reproduction techniques might increase the likelihood of pregnancy and decrease the time interval to conception. In this report, the authors present four patients with endometrial cancer who were treated conservatively with high dose progestin. In all of the cases, the endo-myometrial junctional zone was intact with no evidence of extra-uterine spread on pelvic imaging. A total of seven intracytoplasmic sperm injection and embryo transfer cycles were performed in four patients; five healthy infants were delivered. Two additional spontaneous pregnancies occurred in two patients. During the follow-up period, no recurrence was noted. Although there are limited data, fertility sparing with high dose progestin therapy may be offered to patients with early stage disease and subsequently assisted reproductive techniques may be employed to achieve immediate pregnancy.

TESE-ICSI in patients with non-mosaic Klinefelter syndrome: a comparative study.

There are limited data in the literature on the performance of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) treatment in patients with Klinefelter syndrome. The current study compared TESE-ICSI treatment in patients with non-mosaic Klinefelter syndrome with controls having non-obstructive azoospermia and normal karyotype. Thirty-three consecutive patients (39 TESE-ICSI cycles) with Klinefelter syndrome (study group) and 113 consecutive patients (130 TESE-ICSI cycles) with non-obstructive azoospermia and normal karyotype (control group) were recruited in a private IVF setting. In the two groups, the mean ages of the men at the time of TESE were 32.0 +/- 6.4 and 34.3 +/- 5.8 years respectively (P < 0.05) and the successful sperm recovery rates per total TESE attempts were 56 (22/39) and 44% (57/130) respectively. Similarly, fertilization rates were comparable between the two groups. In the Klinefelter syndrome group, following biopsy and fluorescence in-situ hybridization, a normal karyotype was obtained in 42 of the 71 embryos (59%). The clinical pregnancy and implantation rates in the study and control groups were similar (39, 23 and 33, 26% respectively). In conclusion, patients with non-mosaic Klinefelter syndrome have sperm recovery and pregnancy rates comparable with patients having non-obstructive azoospermia and normal karyotype.