Follicular homocysteine as a marker of oocyte quality in PCOS and the role of micronutrients.

PURPOSE: Does follicular homocysteine predict the reproductive potential of oocytes following FSH stimulation in PCOS women? Can it be modulated by dietary interventions? METHODS: This was a prospective, randomized, interventional clinical study. Forty-eight PCOS women undergoing in vitro fertilization at a private fertility clinic were randomized for a dietary supplementation providing micronutrients involved in homocysteine clearance or no treatment. The supplement was assumed 2 months before stimulation until pick-up day. Monofollicular fluids were collected and frozen. After embryo transfer, the fluids from the follicles generating the transferred embryos were thawed and analyzed. RESULTS: Follicular homocysteine showed a negative correlation with clinical pregnancy both in the whole population (r = - 0.298; p = 0.041) and in controls (r = - 0.447, p = 0.053). The support achieved a non-significantly lower concentration of follicular homocysteine (median [IQR]-7.6 [13.2] vs 24.3 [22.9]). Supplemented patients required far less FSH for stimulation (1650 [325] vs 2250 [337], p = 0.00002) with no differences in the number of oocytes collected, MII rate, and fertilization rate. Supplemented patients enjoyed higher blastocyst rate (55% [20.5] vs 32% [16.5]; p = 0.0009) and a trend for improved implantation rate (64% vs 32%; p = 0.0606). Clinical pregnancy rates were 58% vs 33% in controls (p = ns). CONCLUSION: Follicular homocysteine is a suitable reporter that might be investigated as a tool for oocyte-embryo selection. A diet enriched with methyl donors may be useful in PCOS and supplements may also help. These findings may be also true for non-PCOS women, which warrants investigation. The study was approved by the Acibadem University Research Ethics Committee (2017-3-42). Clinical trial retrospective registration number ISRCTN55983518.

Protocol for developing a core outcome set for male infertility research: an international consensus development study.

STUDY QUESTION: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. WHAT IS KNOWN ALREADY: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. STUDY DESIGN SIZE DURATION: Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health's consensus development conference. PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTERESTS: This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586. TRIAL REGISTRATION DATE: N/A. DATE OF FIRST PATIENT'S ENROLMENT: N/A.

Testis spectroscopy may predict sperm retrieval rate in men with non-obstructive azoospermia undergoing micro-TESE: A pilot study

Objective: To investigate whether prior testis magnetic resonance spectroscopy predicts the success or failure of micro-dissection testicular sperm extraction (micro-TESE) in patients with non-obstructive azoospermia (NOA). Material and Methods: Nine men with NOA who were scheduled for micro-TESE for the first time, 9 NOA men with a history of previous micro-TESE and 5 fertile men were enrolled. All NOA patients and fertile controls underwent testis spectroscopy. A multi-voxel spectroscopy sequence was used. Testicular signals of choline (Cho), creatine (Cr), myo-inositol (MI), lactate, and lipids were analyzed quantitatively and compared with the results of the micro-TESEs. Results: The most prominent peaks were Cho and Cr in the fertile controls and NOA subjects with positive sperm retrieval in the micro-TESE. A high Cho peak was detected in 87% of the NOA men with positive sperm retrieval. NOA men without sperm at the previous micro-TESE showed a marked decrease in Cho and Cr signals. For positive sperm retrieval in micro-TESE, the cut-off value of Cho was 1.46 ppm, the cut-off value of Cr was 1.43 ppm, and the cut-off value of MI was 0.79 ppm. Conclusion: Testis spectroscopy can be used as a non-invasive screening method to predict the success or failure of micro-TESE.

The influence of emotional distress on the outcome of in-vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) treatment among infertile Turkish women.

BACKGROUND: To determine whether the emotional distress of infertile Turkish women is related to social support and influences the outcome of their IVF and/or ICSI treatment. METHODS: The Beck Depression Inventory, State- Trait Anxiety Inventory, and Social Support scales were administered to 104 primary infertile Turkish women before the date of their embryo transfer. Comparisons were made between the women who became pregnant and those who did not following the embryo transfer. RESULTS: Compared to the pregnant women, the non-pregnant women had a greater number of emotional symptoms despite similar levels of social support. Also, the increased severity of depressive symptoms and higher levels of anxiety were predictive of low pregnancy rates. CONCLUSION: The pregnancy rate of infertile Turkish women was associated with emotional distress and low levels of social support were associated with increased emotional distress. Further research is needed to determine the factors and mechanisms that contribute to emotional distress in the treatment of infertility.

Surgery for Benign Gynecological Disorders Improve Endometrium Receptivity.

Regardless of the anatomical locations, some benign gynecological disorders (BGDs) such as peritoneal endometriosis, ovarian endometrioma, adenomyosis, uterine leiomyomas, endometrial polyps, uterine septum, and hydrosalpinges may lead to implantation failure. Despite progress in medical therapies, surgery remains a mainstay of BGDs treatment. Although our knowledge of endometrial receptivity after BGDs surgery is limited, it has allowed for significant improvement in the treatment of female subfertility. Many researchers studied on pregnancy outcome following BGDs surgery, but they did not investigate the possible impact of surgery on endometrial receptivity. They, therefore, concluded that pregnancy rates improved after BGDs surgery based on clinical observations. Many of these clinicians believe that surgical resection of BGDs leads to removal of local mechanical effect over the endometrium. Moreover, they accept that BGDs surgery may inhibit the detrimental signaling and secretion of some molecules from the BGDSs into the endometrium that may lead to favorable effect on the endometrium. However, so far, data from randomized controlled trials or systematic review or meta-analyses to answer the question whether surgical treatment of BGDs can improve endometrial receptivity are lacking. The purpose of this systematic review was to evaluate the results of available publications dealing with the impact of reproductive surgery for BGDs on endometrial receptivity.

Aspiration of ovarian endometriomas before intracytoplasmic sperm injection.

OBJECTIVE: To investigate whether aspiration of ovarian endometriomas before controlled ovarian stimulation (COH) improves intracytoplasmic sperm injection (ICSI) outcomes. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): A prospective analysis of 171 patients with ovarian endometriosis and tubal factor infertility were divided into four groups: aspiration of endometriomas at the beginning of COH in patients with ovarian endometriomas and no history of previous surgery (n = 41) (group 1); nonaspirated endometriomas (n = 40) (group 2); history of ovarian surgery for endometriomas in patients without ovarian endometriomas at the beginning of COH (n = 44) (group 3); and tubal factor infertility (n = 46) (control group 4). INTERVENTION(S): Aspiration of endometriomas. MAIN OUTCOME MEASURE(S): Clinical parameters, characteristics of COH, and ICSI results were analyzed. RESULT(S): We observed higher levels of E(2) on the day of hCG injection after aspiration of endometriomas compared with nonaspirated endometriomas. When we compared all endometriomas and tubal factor (control) groups, we observed a lower number of total follicles (>17 mm) and metaphase II (MII) oocytes in nonaspirated and resected endometrioma groups and a longer duration of COH in the nonaspirated endometrioma group compared with the tubal factor group. Implantation and clinical pregnancy rates were similar among all groups. CONCLUSION(S): In the current study, all patients with endometriomas had significantly lower numbers of MII oocytes compared with those in patients with tubal factor infertility. We propose that aspiration of endometriomas before COH neither reduces the amount of gonadotropins nor increases the number of follicles >17 mm, the number of MII oocytes retrieved, the implantation rates, or the clinical pregnancy rates. Resection of small endometriomas (1-6 cm) may not present any additional benefits to the IVF-ICSI cycle outcomes.

Intrauterine insemination: is the timing correct?

OBJECTIVE: To evaluate the impact of follicle rupture on pregnancy rate in intrauterine insemination. MATERIAL AND METHOD: Retrospective cohort study. Evidence of follicle rupture was assessed by transvaginal ultrasonography following IUI. Two hundred ninety-six couples with unexplained infertility and 121 couples with male factor subfertility were included. Results of 578 cycles were analyzed here. RESULT: Clinical pregnancy rate was 23.5% (64/272) in the group when follicle rupture was evident by transvaginal ultrasonography, while it was only 8.8% (27/306) when follicle rupture was not evident (p < 0.001). CONCLUSION: Postponing IUI until observation of follicle rupture may yield a higher pregnancy rate.

"Chromohysteroscopy" for evaluation of endometrium in recurrent in vitro fertilization failure.

PURPOSE: To assess the efficacy of chromohysteroscopy in detecting endometrial pathologies in recurrent in vitro fertilization (IVF) failure. MATERIALS AND METHODS: Sixty-four patients in whom conventional hysteroscopy did not show any apparent endometrial pathology were included. Five milliliter of 1% methylene blue dye was introduced through the hysteroscopic inlet. Biopsies were obtained both from dark stained and light stained areas. RESULTS: The study group was grouped according to the staining characteristics. Group I included 22 patients in whom focal dark staining was observed. Group II included 41 patients in whom diffuse light blue staining without dark areas was observed. There was no significant difference between two groups in age, smoking, body mass index, number of IVF failure and time to hysteroscopy after the last failure. But, there was a statistically significant difference in the incidence of endometritis between two groups (p=0.007). The power of dark staining for detection of endometritis was calculated as follows: sensitivity 69.2%, specificity 74%, positive predictive value 40.9% and negative predictive value 90.2%. CONCLUSION: Chromohysteroscopy improves the efficacy of hysteroscopy in recurrent IVF failure. Observation of diffuse light blue staining without dark areas strongly suggests a normal endometrium free of endometritis.

Effect of heat-induced hypermotility on pregnancy rate in intrauterine insemination for male factor infertility associated with asthenospermia: a prospective, randomized, controlled study.

OBJECTIVE: To assess the effect of mild heat for the enhancement of sperm fertilizing capacity in intrauterine insemination for male factor infertility associated with asthenospermia. MATERIAL AND METHOD: Prospective, controlled, clinical study. Male factor infertility associated with asthenozoospermia was the criteria for inclusion. Ninety-seven couples were randomized to the study group while 100 couples were randomized to serve as the control group. Semen samples from the study group were processed with Percoll gradient and were left for incubation at 40 degrees C for 2 h. Semen samples from the control group were processed with Percoll gradient method and were incubated at 37 degrees C. Main outcome measure was the pregnancy rate. RESULTS: The mean concentration of total motile sperm (TMS) in the study group was 11.20 +/- 4.22 x 10(6) (range 7-18) after wash with Percoll while was increased to 62.41 +/- 12.49 x 10(6) (range 44-71) after heat treatment. The mean concentration of TMS in the control group was 13.90 +/- 5.66 x 10(6) (range 8-19) after wash with Percoll while was increased to 17.73 +/- 3.67 x 10(6) (range 14-22) after incubation at 37 degrees C. The difference in TMS concentrations between the study and the control group after incubation at different temperatures was statistically significant (p < 0.005). There were 24 pregnancies in the study group, providing a pregnancy rate of 24.7%. In the control group eight pregnancies were achieved (8%) (p = 0.001). CONCLUSION: Mild heat was found remarkably effective in asthenozoospermic males for increasing the concentration of inseminated total motile sperm and the pregnancy rate correspondingly.

Growth hormone co-treatment within a GnRH agonist long protocol in patients with poor ovarian response: a prospective, randomized, clinical trial.

OBJECTIVE: The efficacy of growth hormone co-stimulation to long luteal GnRHa regimen in poor responders to COH for IVF was assessed. METHODS: This prospective, randomized, clinical trial was performed in a private assisted reproduction center. The study involved 61 patients who responded poorly to high dose gonadotropin treatment in their first cycles in the same center. Study group of 31 patients were given growth hormone co-treatment, daily subcutaneous injection of 4 mg from day 21 of preceding cycle along with GnRHa, until the day of hCG. Control group of 30 patients received the same treatment protocol except the growth hormone cotreatment. Primary end-point of the study was the number of oocytes fertilized whereas the pregnancy rate was the secondary end-point. RESULTS: Patients' demographic characteristics did not differ significantly between the two groups. 2PNs in growth hormone co-treatment group was significantly higher than the control group (4.4 +/- 1.8 vs 1.5 +/- 0.9, p < 0.001). Although more pregnancies and more clinical pregnancies with fetal heart beat were achieved in growth hormone group (12/31), compared to the control group (6/30), the difference did not reach to statistical significance. CONCLUSION: Poor responder women undergoing repeated assisted reproduction treatment and co-stimulated with GH achieve more oocytes, higher fertilization rate if growth hormone started in the luteal phase of previous cycle, as compared with women of the same status treated with GnRHa long protocol. The study was unable to show that clinical pregnancy rate was increased significantly.

Intrauterine insemination with double ejaculate compared with single ejaculate in male factor infertility: a pilot study.

The aim of this study was to compare the efficiency of using a double ejaculate with the efficiency of using a single ejaculate for intrauterine insemination in male subfertility. Eligibility for the study was a total motile sperm count between 1 x 10(6) and 5 x 10(6) on postwash sperm analysis. Thirty-nine couples were randomized to the study group, while another 50 couples were randomized to serve as the control group. Males in the study group were asked to produce a second semen sample within 2 hours of the first sample on the day of insemination. In the study group, the mean total motile sperm count in the first sample was 3.83 x 10(6) (SD +/- 0.85 x 10(6); range 1.1-4.9) and 3.99 x 10(6) (SD +/- 0.72 x 10(6); range 0.9-4.4) in the control group. The mean total motile sperm count in the second sample was 3.52 x 10(6) (SD +/- 1.46 x 10(6); range 0.9-3.7) in the study group. The mean total motile sperm count in the final inseminate was 7.35 x 10(6) (SD +/- 1.90 x 10(6); range 2.9-10.6) in the study group. The difference in total motile sperm counts between the study and the control group was statistically significant (P < .001). There were 6 pregnancies in the study group, providing a pregnancy rate of 15.3%, whereas there were 5 pregnancies in the control group, representing a pregnancy rate of 10% (P = .44). We concluded that although it does not increase the pregnancy rate significantly, obtaining a second semen sample when the motile sperm yield of the first semen sample is 1 million to 5 million significantly increases the total motile sperm count in the final inseminate.

Efficiency of follicle-stimulating hormone, commenced in the luteal phase, for overcoming a poor response in assisted reproduction.

AIM: The efficacy of commencement of recombinant follicle-stimulating hormone (recFSH) during the luteal phase in the long-protocol gonadotropin-releasing hormone (GnRH) agonist regimen in poor responders was compared with the conventional protocol in a prospective, randomized, controlled study. METHODS: Forty-two women who responded poorly to previous conventional controlled ovarian hyperstimulation were included in the study. Recombinant FSH (150 IU) was started simultaneously with the GnRH agonist long protocol in the study group. The control group was started recFSH on Day 2 of menstruation in the long-protocol GnRH agonist regimen. The number of metaphase (M) II oocytes, the number of embryos transferred, and the pregnancy rate were analyzed as main outcome measures. RESULTS: Patients in the study group had a higher number of MII oocytes compared with the control group (6.8 vs 3.2, respectively; P < 0.005), received a higher number of embryos (2.7 vs 1.2, respectively; P < 0.05), and had higher pregnancy rates (38% vs 15%, respectively; P < 0.005). CONCLUSIONS: Commencement of recFSH during the luteal phase simultaneously with the long-protocol GnRH agonist regiment in poor responder women produces better results compared with the conventional long-protocol GnRH agonist plus high-dose recFSH regimen.

When virginity does matter: rigid hysteroscopy for diagnostic and operative vaginoscopy--a series of 26 cases.

Virginity in adult women, although a personal decision, is a limiting factor for gynecologists in diagnosis and treatment. This report presents 26 cases of virgin patients with various gynecologic problems: 11 with vaginal bleeding, 7 with heavy discharge and foul odor, 6 with protruding vaginal mass, and 2 with a sensation of vaginal pressure and pain. A rigid hysteroscopy setting was used for diagnostic and operative vaginoscopy. Eleven foreign bodies were removed, mostly clothing fibers and a piece of plastic. In 5 cases, cervical polyps and a subserous myoma were resected and cut into pieces for removal through the hymenal opening. In conclusion, the use of a rigid hysteroscope as a vaginoscope to replace the speculum in adult virgin patients is feasible and introduces an operative option as well.

Luteal start of exogenous FSH in poor responder women.

PURPOSE: To compare the effectiveness of using recFSH commenced in the luteal phase with a long GnRH agonist protocol or in the early follicular phase with a short GnRH agonist protocol, in infertile women designated as poor responders undergoing treatment with assisted reproduction in a prospective, randomized, controlled study. MATERIALS AND METHODS: Forty-two couples undergoing an ICSI cycle of whom female partner diagnosed as poor responder were included in the study. Recombinant FSH was given daily from day 21 of the previous cycle upon initiation of GnRH agonist in the study group. Control group was given FSH on day 2 in a short protocol GnRH agonist regimen. The number of metaphase 2 oocytes was analysed as the main outcome measure; pregnancy rate and clinical pregnancy rate were secondary outcome measures. RESULTS: Patients in the study group had significantly higher number of metaphase 2 oocytes. Although not statistically significantly patients in the study group had higher pregnancy/clinical pregnancy rates, as well. CONCLUSION: This preliminary study shows that luteal start of recFSH simultaneously with long protocol GnRH agonist in poor responder women produced better results comparing to short protocol GnRH agonist plus high dose FSH regimen.