Consult and procedure incidence outcomes following establishment of a fertility preservation program for children with cancer.

PURPOSE: Fertility is a quality of life outcome adversely affected by cancer therapy. Many childhood cancer patients, however, are not offered options to preserve their fertility. Providers acknowledge difficulty discussing impaired fertility to patients due to lack of knowledge of available options. Our objective was to review the impact of a pediatric multidisciplinary fertility preservation program on providers' fertility preservation counseling and discussion of options. METHODS: A retrospective medical chart review was conducted for pediatric cancer patients prior to and following program establishment. Fertility preservation discussions, consults, and incidence were noted. Following filtering and stratification, 198 and 237 patients were seen prior to and following program establishment, respectively. RESULTS: Following program establishment, provider-patient discussions of impaired fertility (p = 0.007), fertility preservation consults (p = 0.01), and incidence of fertility preservation procedures (p < 0.001) increased among patients. Furthermore, the number of patients who received fertility preservation consults after receiving gonadotoxic treatment decreased (p < 0.001). This trend was particularly noted in pre-pubertal and female patients, for whom fertility preservation options are limited without an established program. CONCLUSION: The establishment of a formal program greatly improved access to fertility preservation consults and procedures in children with cancer.

Vaginal versus intramuscular progesterone for luteal phase support in assisted reproductive techniques: a systematic review and meta-analysis of randomized controlled trials.

We aimed to compare the efficacy of vaginal progesterone versus intramuscular progesterone (IMP) for luteal phase support in assisted reproductive techniques (ART). A comprehensive electronic search of four electronic databases (PubMed, Cochrane Library, Scopus, and ISI Web of Science) was performed from inception till August 2019 for randomized controlled trials (RCTs). We included studies performed different ART with the use of vaginal progesterone versus IMP for luteal phase support. Our primary outcome was clinical pregnancy rate. Our secondary outcomes were ongoing pregnancy, miscarriage, live birth rates, and satisfaction in both groups. 15 RCTs met our inclusion criteria with a total of 5656 patients. Our analysis indicated no significant differences between vaginal progesterone and IMP regarding clinical and ongoing pregnancies (RR = 0.90, 95% CI [0.80, 1.00], p = .06), (RR = 0.90, 95% CI [0.76, 1.06], p = .21), respectively. No significant differences were found between both routes of progesterone in miscarriage (p = .98) and live birth (p = .99). Subgroup analysis between fresh and frozen embryo transfer cycles in above outcomes showed no difference between progesterone routes. Vaginal progesterone was significantly associated with more satisfaction compared to IMP (p < .00001). In conclusion, vaginal progesterone can be used an alternative method for luteal phase support instead of IMP in ART.

Revisiting debates of premature luteinization and its effect on assisted reproductive technology outcome.

The impact of the prematurely elevated serum progesterone on the late follicular phase, commonly known as premature luteinization (PL), is a matter of continuing debate. Available evidence supports that serum progesterone ≥ 1.5 ng/ml on the day of ovulation triggering could reduce the pregnancy potential in fresh in vitro fertilization (IVF) cycles by jeopardizing endometrial receptivity. Causes of PL during ovarian stimulation are unclear. Recent studies point toward the daily follicle-stimulating hormone dosage, duration of controlled ovarian stimulation, number of oocytes retrieved, and peak estradiol level as factors affecting the incidence of PL. Emerging data show additional influence on embryo quality. The prevention of PL has been challenging. The key elements in preventing PL include individualization of ovarian stimulation according to patient's ovarian reserve, proper ovulation trigger timing, and use of medications such as corticosteroids and metformin. Embryo cryopreservation with deferred embryo transfer is the established strategy to overcome PL, yet it is an extra burden to the IVF laboratory and increased cost for patients. Herein, we review the up-to-date knowledge of this frequent IVF problem including causes, proposed diagnostic criteria, and its impact on endometrial receptivity, embryo quality, and pregnancy outcomes. The preventive measures and rescue strategies are also discussed.

Foam Sclerotherapy in Pelvic Congestion Syndrome.

Chronic pelvic pain (CPP) is a prevalent condition in middle-aged women that represents a heavy social impact on the quality of life of those females. Treatment of pelvic congestion syndrome is a complex and controversial issue, but treatment can be one of 3 lines: medical therapy, endovascular treatment, and surgical intervention. The endovascular line was first introduced in 1993 and has been popular over other lines of treatment methods. This retrospective study was conducted in a tertiary university hospital over 24 months, from March 2019 to March 2021. Forty patients with PGS were managed by left ovarian vein TCFS. The Institutional Review Board waived the need for ethics approval or informed consent to use anonymized and retrospectively analyzed data. The mean age of enrolled women was 33.80 ± 6.54 years, ranging between 20 and 45 years. Trans-catheter ethanolamine foam embolization is an effective and safe method to treat pelvic and atypical lower limb varices.

Ovarian Stimulation in Patient-oriented Strategies Encompassing Individualised Oocyte Number-4 Category; Antagonist versus Short-agonist Protocols.

Background: Recently POSEIDON (Patient-Oriented Strategies Encompassing Individualized Oocyte Number) classification was proposed to categorize patients with expected poor response to conventional stimulation. Searching for the ideal management of poor responders in IVF is still an active research area. Aims: This study compares GnRH-antagonist and GnRH-agonist short protocols in ICSI cycles for the POSEIDON-4 group. Settings and Design: This retrospective study was conducted in a tertiary infertility unit between January 2016 and December 2020. Materials and Methods: Infertile women who met the criteria for POSEIDON 4 group and underwent fresh ICSI-ET in using GnRH-antagonist and GnRH-agonist short protocols was performed. POSEIDON-4 includes patients ≥ 35 years with poor ovarian reserve markers; AFC < 5 and AMH < 1.2 ng/ml. Statistical Analysis Used: Numerical variables were compared between both groups by student's t test and Mann Whitney test when appropriate. Chi-square test used to compare categorical variables. Multivariate logistic regression models were utilized to adjust for the effect of the different study confounders on live birth rate. Results: One hundred ninety fresh ICSI cycles were analyzed. Of the total cohort, 41.6 % (79) patients pursued antagonist protocol compared to 58.4% (111) underwent short agonist protocol. Fresh embryo transfer was accomplished in 55.7 % (44/79) vs. 61.3 % (68/111), P = 0.44 in antagonist vs. short protocol respectively. Cycle cancellation due to poor ovarian response was encountered in (32.9%vs. 27.9%, P = 0.50) in the antagonist and short groups, whereas no good-quality embryos were developed after ovum pickup in 11.4% vs. 10.8%, P>0.05. Comparable total gonadotropins dose, number of retrieved and mature oocytes, and good-quality embryos were found in both groups. Likewise, clinical pregnancy rate was not different for the antagonist and short groups [11/79 (13.9%) vs. 20/111 (18%), P = 0.45]. The live birth rate was comparable between both groups (8.9% vs. 10.8%, P = 0.659) for antagonist and short groups respectively. No significant impact for the protocol type on live birth rate was revealed after adjusting to cycle confounders in multivariate analysis (OR: 0.439, 95%CI 0.134-1.434, P = 0.173). Conclusion: This study shows comparable pregnancy outcomes for antagonist and short-agonist protocols in IVF/ICSI cycles for POSEIDON-4 category.

The Impact of High Circulating Anti-Müllerian Hormone on Endometrial Thickness and Outcome of Assisted Reproductive Technology in Women with Polycystic Ovarian Syndrome: A Cohort Study.

Background: Elevated circulating anti-Müllerian hormone (AMH) in women with the polycystic ovarian syndrome (PCOS) has been found to have a detrimental effect on endometrial function. This may adversely affect the outcome of in vitro fertilisation (IVF) in PCOS women. Aims: To investigate the impact of high serum AMH concentrations on endometrial thickness (ET) and the outcome of IVF in women with PCOS. Settings and Design: This retrospective cohort study included all PCOS women who underwent fresh IVF\intracytoplasmic sperm injection cycles between January 2016 and December 2021 in one major IVF centre. Materials and Methods: PCOS diagnosis was based on Rotterdam criteria, and participants were identified from centre database. All women received antagonist protocol. Primary outcomes were trigger-day ET and live birth rate (LBR). Circulating AMH was correlated with ET and ovarian response. Statistical Analysis Used: AMH levels were compared between women with and without live birth. ET and LBRs were compared between women with AMH <7.0 ng/ml versus those with AMH ≥7.0 ng/ml. Results: The study included 102 PCOS women, of which six were excluded due to poor response (n = 4), hyperresponse (n = 1) or fertilisation failure (n = 1). Of the remaining 96 women, 42 (43.8%) achieved a live birth. There was no statistically significant (P > 0.05) correlation between AMH and ET. Mean ± standard deviation AMH concentration was not significantly (P > 0.05) different between women with live birth (6.5 ± 3.4 ng/ml) and those without (6.5 ± 2.4 ng/ml). High AMH positively correlated with the number of oocytes retrieved, metaphase II oocytes and embryos (P = 0.003, 0.006 and 0.006, respectively). There was no statistically significant (P > 0.05) difference in ET or LBR between women with AMH <7.0 ng/ml (n = 72; ET, 10.7 ± 1.8 mm; LBR, 45.8% [33/72] versus those with AMH ≥7.0 ng/ml (n = 24; ET, 10.8 ± 1.7 mm; LBR, 37.5% [9/24]). Conclusions: High circulating AMH in PCOS women does not seem to negatively affect ET or LBRs during assisted reproductive technology.

Current Insights and Latest Updates in Sperm Motility and Associated Applications in Assisted Reproduction.

Spermatozoon is a motile cell with a special ability to travel through the woman's reproductive tract and fertilize an oocyte. To reach and penetrate the oocyte, spermatozoa should possess progressive motility. Therefore, motility is an important parameter during both natural and assisted conception. The global trend of progressive reduction in the number and motility of healthy spermatozoa in the ejaculate is associated with increased risk of infertility. Therefore, developing approaches for maintaining or enhancing human sperm motility has been an important area of investigation. In this review we discuss the physiology of sperm, molecular pathways regulating sperm motility, risk factors affecting sperm motility, and the role of sperm motility in fertility outcomes. In addition, we discuss various pharmacological agents and biomolecules that can enhance sperm motility in vitro and in vivo conditions to improve assisted reproductive technology (ART) outcomes. This article opens dialogs to help toxicologists, clinicians, andrologists, and embryologists in understanding the mechanism of factors influencing sperm motility and various management strategies to improve treatment outcomes.

Does type of cancer affect ovarian response in oncofertility patients?

INTRODUCTION: To evaluate the influence of type of cancer and cancer itself on the ovarian response during controlled ovarian stimulation (COS) for fertility preservation (FP). MATERIALS AND METHODS: This was a retrospective cohort study performed at a single academic tertiary-care infertility center. Women diagnosed with cancer who underwent COS with GnRH antagonist protocol between January 2009 and December 2018 were included in this study. Patients were categorized into three groups; breast/gynecologic, hematologic, and other cancers. We secondarily compared the COS parameters and ovarian reserve markers in oncofertility cases against non-cancer patients who pursued FP for deferred reproduction. The primary outcome was number of mature oocytes. Secondary outcomes included oocyte yield (number of retrieved oocytes/number of follicles aspirated at time of retrieval) and oocyte-maturity index, defined as number of mature oocytes/total oocytes retrieved. RESULTS: A total of 96 cancer patients were referred for FP counseling before starting their anti-cancer therapy. Clinical characteristics and ovarian response parameters were comparable between the three groups. Type of cancer was not a predictor for number of mature oocytes (p = 0.329), oocyte-maturity index (p = 0.815), or oocyte yield, (p = 0.161) after adjustment to cycle covariates. Moreover, cancer did not have impact on the number of mature oocytes (p = 0.699), oocyte-maturity index (p = 0.251) and oocyte yield (p = 0.094). DISCUSSION: There is no difference observed in outcomes of ovarian stimulation based on primary cancer diagnosis in oncofertility patients undergoing FP. Interestingly, no significant impact for cancer itself was observed on ovarian reserve or response to gonadotrophins stimulation.

Effect of Metformin on Premature Luteinization and Pregnancy Outcomes in Intracytoplasmic Sperm Injection-Fresh Embryo Transfer Cycles: A Randomized Double-Blind Controlled Trial.

BACKGROUND: Premature luteinization (PL) is not unusual in in vitro fertilization (IVF) and could not be wholly avoided by using either gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonist regimens. The study aims to evaluate metformin's efficacy in preventing PL in fresh GnRH antagonist intracytoplasmic sperm injection (ICSI) cycles with cleavage-stage embryo transfer. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial was conducted in a tertiary university IVF center. We recruited infertile women who were scheduled to perform their first or second ICSI trial. Eligible women were recruited and randomized in a 1:1 ratio into two groups. Metformin was administered in a dose of 1500 mg per day since the start of contraceptive pills in the cycle antecedent to stimulation cycle until the day of ovulation triggering, while women in the placebo group received a placebo for the same regimen and duration. The primary outcome was the incidence of PL, defined as serum progesterone (P) on the triggering day ≥1.5 ng/mL. Secondary outcomes comprised the live birth, ongoing pregnancy, implantation, and good-quality embryos rates. RESULTS: The trial involved 320 eligible participants (n=160 in each group). Both groups had comparable stimulation days, endometrial thickness, peak estradiol levels, number of oocytes retrieved, and number of mature oocytes. Metformin group experienced lower level of serum P (P<0.001) and incidence of PL (10 vs. 23.6%, P=0.001). Moreover, lower progesterone/estradiol (P/E) ratio and progesterone to mature oocyte index (PMOI) (P=0.002 and P=0.002, respectively) were demonstrated in women receiving metformin. Metformin group generated a better rate of goodquality embryos (P=0.005) and ongoing pregnancy (43.8 vs. 31.8%, P=0.026). A similar trend, though of borderline significance, was observed in the live birth rate in favor of metformin administration (38.15 vs. 27.5%, P=0.04). CONCLUSION: Metformin could be used in patients with potential PL to improve fresh cycle outcomes by preventing PL (Registration number: NCT03088631).

Progesterone/Oestradiol ratio can Better Predict Intracytoplasmic Sperm Injection Outcomes than Absolute Progesterone Level.

BACKGROUND: Several parameters were proposed to predict the impact of premature luteinization on intracytoplasmic sperm injection (ICSI) outcomes such as isolated progesterone (P) level, progesterone to oocyte ratio, and progesterone/estradiol ratio (P/E2). AIM: The aim of this study is to compare the predictive value of P/E2 ratio and isolated P level on the ovulation triggering day for pregnancy outcomes in fresh GnRH antagonist ICSI cycles. SETTINGS AND DESIGN: A retrospective cohort study conducted in a university-affiliated in vitro fertilization center between January 2017 and April 2019. METHODS: The study included women who underwent their first- or second-ranked GnRH antagonist ICSI cycles with day-3 embryo transfer. P/E2 ratio was calculated as (P [ng/mL] × 1000)/E2 (pg/mL). Cutoff values of ≥1.5 ng/ml for high P (HP) and ≥0.55 for HP/E2 ratio were chosen based on the literature. STATISTICAL ANALYSIS: A receiver operating curve was performed to detect the predictability of serum P/E2 and P for the ongoing pregnancy rate. First, patients were divided according to either P level (low P < 1.5 ng/mL and HP ≥1.5 ng/mL) or P/E2 ratio (low P/E2 <0.55 and HP/E2 ≥ 0.55). Patients were further divided into four subgroups: (Group A: HP and HP/E2 ratio, Group B: low P and low P/E2 ratio, Group C: HP only, and Group D: HP/E2 only). A multivariate regression analysis models were used to account for the effect of the cycle confounders on the likelihood of pregnancy. RESULTS: A total of 402 ICSI cycles were analyzed. The area under the curve was 0.67 and 0.59 for P/E2 and P, respectively. P/E2 showed a significant association with ongoing pregnancy (adjusted odds ratios [aOR]: 0.409, 95% confidence interval [CI] 0.222-0.753, P = 0.004) while HP revealed no significant predictive value (aOR: 0.542, 95% CI 0.284-1.036, P = 0.064) after the multivariate analysis. CONCLUSIONS: P elevation may not present as an independent predictor for cycle outcomes. P/E2 ratio has a better prognostic value than P alone in predicting pregnancy of GnRH antagonist cycles.

Fertility Preservation in Women: Indications and Options for Therapy.

Fertility preservation (FP) is a vital issue for individuals in either reproductive or prepubescent stage of life when future fertility may be compromised. The objective of any FP intervention is to minimize or eliminate primary disease burden and to ensure maintaining or preserving reproductive health. Fertility potential can be affected by cancer therapy and numerous other factors, including advancing age, metabolic conditions, autoimmune diseases, specific surgical interventions, and sex affirmation procedures. A paradigm shift focusing on quality-of-life issues and long-term survivorship has emerged, especially because of advances in cancer diagnostics and treatment. Several FP techniques have been widely distributed, while others are still in the research stage. In addition, specific procedures and some potentially fertoprotective agents are being developed, aiming to minimize the hazards of gonadal damage caused by cancer therapy and decrease the need for more costly, invasive, and time-consuming FP methods. This review highlights the advances, indications, and options for FP, both experimental and well-established, in females of various age groups. An electronic search in PubMed, Embase, and Google Scholar databases was conducted, including retrospective studies, prospective clinical trials, meta-analyses, original reviews, and online abstracts published up to June 30, 2019. The search terms used included fertility preservation, oncofertility, embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation. The meeting proceedings of the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology were also hand searched.

Higher clinical pregnancy rate with in-vitro fertilization versus intracytoplasmic sperm injection in treatment of non-male factor infertility: Systematic review and meta-analysis.

OBJECTIVE: To evaluate the evidence about in-vitro fertilization (IVF) versus intracytoplasmic sperm injection (ICSI) for the treatment of non-male factor infertility. DATA SOURCES: Electronic databases searched using the following MeSH terms (Sperm Injection, Intracytoplasmic) AND (in Vitro Fertilisation) AND (Infertility). METHODS OF STUDY SELECTION: All RCTs included infertile patients due to non-male factors underwent IVF or ICSI were considered for this meta-analysis. One-thousand twenty-two studies were identified of which 20 studies deemed eligible for this review. DATA EXTRACTION: Three independent authors extracted the relevant data from included studies. The study outcomes were pooled in the form of relative risk (RR) and 95 % confidence interval (CI) using Mantel-Hansel method. The main outcome measures are the fertilization rate, the implantation rate, the clinical pregnancy rate (CPR), the total fertilization failure and the live birth rate. RESULTS: Regarding the fertilization rate, the pooled estimate did not favour either IVF or ICSI group (RR = 0.94; 95 %CI [0.82, 1.07]; p = 0.34). However, IVF significantly increased the CPR than ICSI (RR = 1.28, 95 %CI [1.11, 1.49]; p = 0.001). The overall effect estimate did not favor either of two groups regarding the implantation rate (RR = 1.25, 95 % CI [0.92, 1.68], p = 0.15). Similarly, no difference between both groups regarding the live birth rate (RR = 1.08, 95 % CI [0.79, 1.49]; p = 0.62). CONCLUSIONS: No difference between ICSI and IVF regarding fertilization rate per oocytes, implantation rate and live birth rate in the treatment of non-male factor infertility, while IVF has significantly higher clinical pregnancy rate and higher risk of total fertilization failure.