International Journal Of Fertility and Sterility
Volume:15 Issue: 2, Apr-Jun 2021

The aim of this study is to review current indications to diagnostic and/or operative hysteroscopy in primary and secondary infertility, as well as to determine its efficacy in improving fertility.

We gathered available evidence about the role of hysteroscopy in the management of various infertility conditions. Literature from 2000 to 2020 that pertained to this topic were retrieved and appropriately selected.

Hysteroscopy does not appear as a first line diagnostic procedure for every clinical scenario. However, its diagnostic sensitivity and specificity in assessing intrauterine pathology is superior to all other non-invasive techniques, such as saline infusion/gel instillation sonography (SIS/GIS), transvaginal sonography (TVS) and hysterosalpingography (HSG). Hysteroscopy allows not only a satisfactory evaluation of the uterine cavity but also, the eventual treatment of endocavitary pathologies that may affect fertility both in spontaneous and assisted reproductive technology (ART) cycles.

Hysteroscopy, due to its diagnostic and therapeutic potential, should be regarded as a necessary step in infertility management. However, in case of suspected uterine malformation, hysteroscopy should be integrated with other tests [three-dimensional (3D) ultrasound or magnetic resonance imaging (MRI)] for diagnostic confirmation.

Deep infiltrating endometriosis (DIE) is the most aggressive of the three phenotypes that constitute endometriosis.It can affect the whole pelvis, subverting the anatomy and functionality of vital organs, with an important negativeimpact on the patient’s quality of life. The diagnosis of DIE is based on clinical and physical examination, instrumentalexamination, and, if surgery is needed, the identification and biopsy of lesions. The choice of the best therapeuticapproach for women with DIE is often challenging. Therapeutic options include medical and surgical treatment, andthe decision should be dictated by the patient’s medical history, disease stage, symptom severity, and personal choice.Medical therapy can control the symptoms and stop the development of pathology, keeping in mind the side effectsderived from a long-term treatment and the risk of recurrence once suspended. Surgical treatment should be proposedonly when it is strictly necessary (failed hormone therapy, contraindications to hormone treatment, severity of symptoms,infertility), preferring, whenever possible, a conservative approach performed by a multidisciplinary team. Alltherapeutic possibilities have to be explained by the physicians in order to help the patients to make the right choiceand minimize the impact of the disease on their lives.

To evaluate the effects of vitamin D (vitD) supplement on uterine fibroid growth. A randomized blinded clinical trial was conducted at a tertiary university-based hospitalfrom August 2017 to September 2018. Totally, 204 women were enrolled into the study. They had at least one uterinefibroid >10 mm on transvaginal ultrasound and their vitD level was insufficient (i.e. 20-30 ng/ml). The interventiongroup was treated with vitD 50000 U supplements for two months. After 2 months, ultrasound screening and vitDlevel measurement was done in both groups. At first, the mean serum vitD levels in intervention and control group were 23.62 and 23.20 ng/ml, respectively.After 8 weeks, the mean serum vitD levels in the control and intervention group were 22.72 and 28.56 ng/mlrespectively (p <0.05). Also, mean fibroma diameter in the intervention group before and after 8 weeks of vitD supplementationwas 43 ± 4.68 and 42.6 ± 1.31 mm, respectively. Mean uterine fibroid diameter in the control group whichdid not receive vitD supplements, before and after 8 weeks was 41.98 ± 5.25 and 47.81 ± 3.42 mm, respectively. Thevariation in the mean size of the uterine fibroid between the control and intervention group which was respectivelyabout 5.83 mm increase and 0.48 mm decrease, was significant (p <0.001). Our results showed that vitD supplementation prevents fibroid growth. It seems that vitD supplementis a simple, safe and inexpensive modality for leiomyoma growth prevention (Registration number:IRCT201703122576N15).

Polycystic ovary syndrome (PCOS) is associated with metabolic disorder as well as infertility. Manytraditional remedies have been reported to show estrogenic and antioxidant potential. Bee pollen is a natural compound,reported as one such remedy. The present study aimed to investigate the effects of BP extract and metformin(MET) on estradiol (E2) and testosterone (T) levels, apoptotic markers, and total antioxidant capacity (TAC) inaratmodel of PCOS. In this experimental study, 54 female Wistar (n=6/group) rats received 2 mg of estradiolvalerate (EV) intramuscularly and 6 additional rats were considered the control without EV injection. The rats weretreated with BP (50, 100, and 200 mg/kg), MET (300 mg/kg) and BP+MET (50 BP+300 MET, 100 BP+300 MET,and 200 BP+300 MET mg/kg). Serum levels of E2 and T were assessed by ELISA method. TAC of serum was alsodetermined. The expressions of Bcl-2, Bax and Caspase-3 (Cas-3), and Sirt-1 genes were evaluated by real-time polymerasechain reaction (PCR). Data were statistically analyzed using one-way ANOVA. In the untreated PCOS group E2 and T levels (p <0.01), and Bcl-2 (P=0.007) expression were increased, but TAC(P=0.002) and expression of Bax (P=0.001), Cas-3 and Sirt1 (p <0.01) were decreased significantly. The levels of E2 and T,as well as the expressions of Bcl-2 were decreased in all treated groups compared to the untreated PCOS group (p <0.01). Onthe other hand, TAC and expression of Bax, Cas-3 and Sirt1 were increased in the BP- and MET-treated groups (p <0.05). BP and MET synergistically improved serum E2, T and TAC levels, and expression of apoptotic genes.

Premature luteinization (PL) is not unusual in in vitro fertilization (IVF) and could not be whollyavoided by using either gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonist regimens. The studyaims to evaluate metformin’s efficacy in preventing PL in fresh GnRH antagonist intracytoplasmic sperm injection(ICSI) cycles with cleavage-stage embryo transfer. This randomized, double-blind, placebo-controlled trial was conducted in a tertiary universityIVF center. We recruited infertile women who were scheduled to perform their first or second ICSI trial. Eligiblewomen were recruited and randomized in a 1:1 ratio into two groups. Metformin was administered in a dose of 1500mg per day since the start of contraceptive pills in the cycle antecedent to stimulation cycle until the day of ovulationtriggering, while women in the placebo group received a placebo for the same regimen and duration. The primaryoutcome was the incidence of PL, defined as serum progesterone (P) on the triggering day ≥1.5 ng/mL. Secondaryoutcomes comprised the live birth, ongoing pregnancy, implantation, and good-quality embryos rates. The trial involved 320 eligible participants (n=160 in each group). Both groups had comparable stimulationdays, endometrial thickness, peak estradiol levels, number of oocytes retrieved, and number of mature oocytes. Metformingroup 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 goodqualityembryos (P=0.005) and ongoing pregnancy (43.8 vs. 31.8%, P=0.026). A similar trend, though of borderlinesignificance, was observed in the live birth rate in favor of metformin administration (38.15 vs. 27.5%, P=0.04). Metformin could be used in patients with potential PL to improve fresh cycle outcomes by preventing PL(Registration number: NCT03088631).

The objective of this study was to investigate serum levels of anti-Müllerian hormone (AMH) innormal-ovulatory infertile women with polycystic ovarian morphology (PCOM) and their association with ovarianhyper-response. This prospective cohort study was carried out on 100 infertile women with PCOM whowere treated with an antagonist/agonist triggered stimulation protocol at Shahid Akbar-Abadi Hospital IVF Centre,Tehran, Iran. Serum AMH levels were measured before starting the assisted reproductive technology (ART) cycleand the ovarian hyper-response was evaluated by retrieved oocyte numbers, ooestradiol levels on the triggeringday, and the incidence of ovarian hyper-stimulation syndrome (OHSS) clinical signs and symptoms. Logistic regressionand the area under the curve (AUC) were used to estimate the effects of AMH and the accuracy of the test. Receiver operating characteristic (ROC) curve analysis showed that AMH could significantly predict ovarianhyper-response in PCOM patients (AUC=0.73). The estimated threshold value was 4.95 ng/ml, with a specificityof 74.58% (95% confidence interval [CI]: 50.85, 93.22) and sensitivity of 73.17% (95% CI: 48.78, 92.68). Logisticregression results showed a significant interaction between AMH and body mass index (BMI, P=0.008), which indicatedthat BMI had a moderation effect. Individualized stimulation protocols for patients with isolated PCOM and AMH greater than 4.95 ng/mlmay significantly reduce the chances of developing OHSS. However, the AMH cut-off values to predict ovarian hyperresponsediffer for different BMI categories among PCOM patients; thus, it becomes a more precise predictive markerwith increasing BMI.

Polycystic ovary syndrome (PCOS) is the known endocrinopathy disorder in the reproductive phase ofwomen’s life. More than half of the women with PCOS suffer from obesity which impacts the ovarian functions byleptin levels. Here the R223Q and P1019P polymorphisms of leptin receptor (LEPR) gene were examined in PCOSpatients of Kurdish women from west of Iran. In this case-control study, one hundred women with PCOS and 100 healthy women bearingsimilar age range were selected based on Rotterdam diagnostic criteria. Polymerase chain reaction-restriction fragmentlength polymorphism (PCR-RFLP) method was used to genotype polymorphisms LEPR (R223Q and P1019P),by respectively the BsaWI and NcoI restriction enzymes. Pearson’s chi-square (χ2) test was used to analyze the variationin genetic distributions and unconditional logistic regression model was used to calculate the odds ratio (OR;95% CI). Genotype frequencies of the R223Q and P1019P polymorphisms showed significant difference between thepatients with PCOS compared to the controls. G allele (R223Q) reduced the risk of PCOS about 0.49-fold (p <0.001).While, T allele (P1019P) increased the risk of PCOS 2.69-fold (p <0.001). It can be concluded that the R223Q and P1019P polymorphisms showed a significant association withPCOS susceptibility risk. It seems that G allele (R223Q) with reducing OR had a protective effect on this syndrome,while T allele (P1019P) with increasing OR was a risk factor for PCOS.

In vitro fertilization (IVF) is a useful assisted reproductive technology to achieve pregnancy in infertilecouples. However, it is very important to optimize the success rate after IVF by controlling for its influencing factors.This study aims to classify successful deliveries after IVF according to couples’ characteristics and available data onoocytes, sperm, and embryos using several classification methods. This historical cohort study was conducted in a referral infertility centre located inTehran, Iran. The patients’ demographic and clinical variables for 6071 cycles during March 21, 2011 to March20, 2014 were collected. We used six different machine learning approaches including support vector machine(SVM), extreme gradient boosting (XGBoost), logistic regression (LR), random forest (RF), naïve Bayes (NB),and linear discriminant analysis (LDA) to predict successful delivery. The results of the performed methods werecompared using accuracy tools. The rate of successful delivery was 81.2% among 4930 cycles. The total accuracy of the results exposed RFhad the best performance among the six approaches (ACC=0.81). Regarding the importance of variables, total numberof embryos, number of injected oocytes, cause of infertility, female age, and polycystic ovary syndrome (PCOS) werethe most important factors predicting successful delivery. A successful delivery following IVF in infertile individuals is considerably affected by the number ofembryos, number of injected oocytes, cause of infertility, female age, and PCOS.

Reactive oxygen species (ROS) play a crucial role in etiology of DNA fragmentation and lipid peroxidationin sperm, leading to infertility in men. The silent information regulators SIRT1 and SIRT3 are members of thesirtuins protein family known to be involved in cancer genetics, aging and oxidative stress responses. The aim ofthisstudy is to determine the correlation between SIRT1 and SIRT3 with antioxidants, oxidative stress biomarkers, andDNA fragmentation in the semen of asthenoteratozoospermic and normozoospermic men. In this case-control study, after spermogram analysis the specimens were divided intotwo groups, normozospermic (n=40) and asthenoteratozoospermic (n=40), according to World Health Organization(WHO) standards. Sperm DNA fragmentation was evaluatedusing the sperm chromatin dispersion (SCD) test.Catalaseactivity was measured using the Aebi spectrophotometeric method. Total antioxidant capacity (TAC) level and superoxidedismutase (SOD) activitywere measured by using commercially available colorimetric assays. Enzyme-linkedimmune sorbent assay (ELISA) was used to measure SIRT1 and SIRT3 protein levels of seminal plasma. Malondialdehyde(MDA) level in seminal plasma was determined by high-performance liquid chromatography (HPLC). The asthenoteratozoospermic group had significantly lower catalase and SOD activities and TAC levels incomparison with the normozoospermic group (p <0.001).The percentage of DNA fragmentation and MDA level in theasthenoteratozoospermic group were remarkably higher than in the normozoospermic group. The SIRT1 and SIRT3protein levels in seminal plasmawere remarkably lower in asthenoteratozoospermic group than the normozoospermicgroup (p <0.001). The results of this study suggest that SIRT1 and SIRT3 protein levels are negatively correlated withoxidative stress and DNA fragmentation in semen. The low levels of SIRT1 and SIRT3 in asthenoteratozoospermicmen may lead to an increase in oxidative stress, DNA fragmentation, and lipid peroxidation that eventually result inimmotile and immature spermatozoa (asthenoteratozoospermia).

We aimed to investigate the effect of low-intensity endurance training (LIET) and high-intensity intervaltraining (HIIT) on sperm parameters, chromatin status, and oxidative stress in a rat model of non-alcoholic fattyliver disease (NAFLD). For this experimental study, we divided 40 male Wistar rats into four groups (control, sham,HIIT and LIET) according to diet treatment and exercise training protocol. Liver triglycerides, sperm parameters,sperm lipid peroxidation (BODIPY C11 probe) and chromatin status [chromomycin A3 (CMA3)], and acridine orange[AO] staining) were assessed in these groups at the end of the study. The mean liver triglyceride values significantly improved in both the LIET and HIIT groups compared tothe control and sham groups. The mean of testicular volume, sperm concentration, motility, intensity of sperm lipidperoxidation and DNA damage were similar within groups. While, the mean percentage of sperm lipid peroxidationand protamine deficiency were significantly higher in the LIET and HIIT groups compared to the control group. Both LIET and HIIT in the rat NAFLD model had no adverse effects on testicular morphometric parameters,sperm concentration, motility, and DNA integrity. However, the mean sperm lipid peroxidation and protaminedeficiency were significantly higher in both exercise groups. Our study suggests that exercise or antioxidant supplementationcould minimise the adverse effects of oxidant by-products of exercise.

Vascular endothelial growth factor (VEGF) and the corresponding receptors play key role in vasculogenesisand angiogenesis processes. VEGF is one of the prime candidates in regulating embryo implantation byincreasing vascular permeability. VEGF receptor-2, also called Flk-1/KDR, is one of the prime receptor which isactively involved in the execution of various functions of VEGF. However, precise role of this receptor during earlygestation period is yet to be addressed. In the present study, expression of Flk-1/KDR during peri-implantation miceuterus as well as fetal-maternal tissues from day 4-day 7 (D4-D7) of gestation was investigated. In this experimental study, localization of Flk-1/KDR was investigated by immunohistochemistryand immunofluorescence techniques, in paraffin embedded tissue sections. Flk-1/KDR protein and mRNAexpressions were investigated by western blotting and quantitative reverse transcription polymerase chain reaction(qRT-PCR), respectively. Effects of ovarian steroids on expression of Flk-1/KDR were also assessed by estrogen andprogesterone antagonist treatment. Uterine tissue on D4 showed strong expression of Flk-1/KDR in luminal and uterine glandular epithelium.On D5 and D6, differential expression of Flk-1/KDR was evidenced in certain cell types of the embryo, maternaltissues and fetal-maternal interface with varied intensity. Flk-1/KDR was specifically expressed in the ectoplacentalcone (EPC) and various cells of the embryo on D7. Flk-1/KDR expression was not evidenced in the estradiol-17β (E2)and progesterone (P4) antagonist treated uterus. Western blotting result revealed presence of Flk-1/KDR protein inthe all gestation days, except antagonist treated uterus. qRT-PCR analysis showed significant increase of Flk-1/KDRmRNA transcript on D6 and D7. Spatial-temporal expression of Flk-1/KDR during peri-implntation period in mice uterus especially in thefeto-maternal interface was observed. This spatio-temporal specificity as well as increased expression of Flk-1/KDRcould be one of the determinants for establishment of fetal-maternal cross talk during the critical period of development.