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To explore the association of leukemia inhibitory factor receptor (LIFR) gene variant rs3099124, ovarian steroids, and leukemia inhibitory factor with unexplained infertility in Pakistani females. A case–control investigation in which eighty-one (81) females with unexplained infertility and one hundred and sixty-two (162) fertile counterparts (age and body mass index compared) were recruited between October 2016 and 2018. Ten milliliters of venous blood was collected from all participants. "Genomic DNA" was taken out from lymphocytes in peripheral blood samples. "Tetra Amplification Refractory Mutation System Polymerase Chain Reaction (T-ARMS-PCR)" was constructed through software "Primer-I". Amplification was carried out by "T-ARMS-PCR" followed by subsequent sequencing for confirmation and extensive consonance. Estradiol, Progesterone and Leukemia Inhibitory Factor (LIF) were measured in serum by ELISA. Statistically significant difference was noticed in genotype frequency in "LIFR-gene variant; rs3099124" (χ2 = 28.222, P value < 0.01) between research participants. Although, rs "3099124" "AA" (OR = 0.000; 95%CI = 0–0) and "GA" genotypes (OR = 0.525; 95%CI = 0.226–1.22) showed non-significant safety/protection against unexplained infertility yet minor/risk allele "A" frequency was greater in women with unexplained infertility suggesting a possible explanation of implantation failure. LIF concentration varied between fertile and infertile groups (χ2 = 9.857, P < 0.05) revealing significant threat of unexplained infertility in women with decreased LIF concentration (OR = 2.316, 95%CI = 1.214–4.416). Progesterone was significantly related to unexplained infertility in both study groups (χ2 = 20.347, P < 0.05). High progesterone reduced the possibility of unexplained infertility (OR = 0.306; 95% CI = 0.166–0.567). LIFR gene variation (rs3099124) and reduced LIF secretion may cause implantation failure in women with unexplained infertility. [ABSTRACT FROM AUTHOR]

This article reviews the evidence regarding the safety and efficacy of intra-cytoplasmic sperm injection (ICSI). It provides evidence-based clinical and laboratory guidelines and recommendations for use of ICSI within an assisted reproductive technology (ART) service. The guidelines address the evidence for the use of ICSI rather than conventional IVF (cIVF); the use of ART techniques supplementary to ICSI; and risks associated with ICSI. This article is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate, taking into account the needs and medical history of the patient, available resources, and institutional or clinical practice limitations. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated hysterosalpingography (HSG) in general, and specifically with an oil-soluble contrast medium, directly increases pregnancy rates. Decision modelling was performed to compare fertility management using three HSG diagnostic strategies: (i) water-soluble contrast medium (WSCM)-HSG; (ii) Lipiodol® Ultra Fluid (LUF)-HSG; and (iii) No HSG, for women aged ≤39 years with unexplained infertility. Four reimbursement scenarios were modelled to reflect the various funding arrangements across the regions of the United Kingdom. Compared with WSCM-HSG, the live birth rates after 24 months increased by 3.4% with LUF-HSG and decreased by 2.7% with no HSG. From a patient perspective, fertility management with LUF-HSG is the most cost-effective strategy with cost-savings ranging from £299 to £857 per patient depending on the funding arrangement for IVF. From an NHS perspective, fertility management with LUF-HSG is cost-effective when 2 or more IVF cycles are NHS-funded. If none of the IVF cycles are NHS-funded, fertility management with LUF-HSG can be considered cost-effective if society is willing to pay £8,353 for an additional live birth. The findings from this analysis suggest that fertility management with WSCM-HSG is cost-effective compared to no HSG and LUF-HSG is the most cost-effective with increased live birth rates after 24 months. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of granulocyte colony stimulating factor (GCSF) on fertility outcomes in women with unexplained infertility after intrauterine insemination (IUI). This study is a randomised clinical trial that was conducted on unexplained infertile women referred to infertility Clinic in Yasuj, Iran. All participants were stimulated by letrozole, clomiphene and HMG during the cycle. When at least one follicle was greater than 18 mm, 5000 IU hCG intramuscularly was administered for ovulation induction and then IUI was performed 34-36 hours later. In GCSF group, 300 μg GCSF subcutaneously administrated in two days after IUI. Control group received routine IUI. The main outcome measures were biochemical pregnancy, clinical pregnancy, abortion and ongoing pregnancy rate. Our results showed no statistically significant difference in the biochemical pregnancy (16.3% vs. 12.2%; P=.56), clinical pregnancy (16.3% vs. 8.2%; P=.21), abortion (0 vs. 2.04%; P=.55) and ongoing pregnancy rates (8.2% vs. 14.2%; P=.32) between the control and the G-CSF groups. The results of the current study suggest that systemic administration of 300 μg GCSF in the two days after receiving IUI in patients with unexplained infertility does not offer any beneficial clinical related implantation, and pregnancy rates. IRCT registration number: IRCT20160524028038N4 Impact statementWhat is already known on this subject? Unexplained infertility means to the inability of couples in pregnancy after a year without obvious male and female infertility factors. Some patients have not been justified in endometrial function, which leads to the defect of the dialogue between the foetus and endometrium and may lead to implantation failure. Granulocyte colony stimulating factor is produced at the maternal-foetal interface during embryo implantation and is the main part of the uterine-cytokine network that is needed to create and maintain pregnancy.What do the results of this study add? The current study suggests that systemic administration of 300 μg granulocyte colony stimulating factor in the two days after receiving IUI in patients with unexplained infertility does not offer any beneficial clinical related implantation and pregnancy rates.What are the implications of these findings for clinical practice and/or further research? These results may not be generalised to all patients and more randomised controlled trials are needed for the comparison of granulocyte colony stimulating factor effects on women with thin and normal endometrial thickness, efficacy, side effects, and pregnancy outcomes of the intrauterine perfusion versus systemic subcutaneous administration of granulocyte colony stimulating factor in unexplained infertility treated with intrauterine insemination. [ABSTRACT FROM AUTHOR]

The present study aims to evaluate the role of follicular fluid (FF) and serum (s) total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) on the etiopathogenesis of unexplained infertility (UI) and intracytoplasmic sperm injection-embryo transfer (ICSI-ET) success. Twenty UI patients and 20 controls with male factor undergoing an ICSI-ET cycle were recruited. FF samples aspirated from mature follicles and blood samples collected just before the oocyte retrieval were stored until analysis. Embriyo quality and implantation, clinical pregnancy and living birth rates were evaluated. FF-TOS and FF-OSI of the UI patients were higher than the control group. s-TOS and s-OSI were significantly increased in the UI group compared to the control group. However, only s-TOS was positively associated with UI diagnosis after age-adjustment. FF-OSI was negatively associated with embryo quality in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI on implantation, clinical pregnancy and live birth rate was observed. In conclusion, especially s-TOS can have a partial role in the etiopathogenesis of UI. High FF-OSI can decrease the quality of embryo in patients with UI. What is already known? Total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), which is the ratio of TOS to TAS, provide a broad overview of redox status. What do the results of this study add? An elevated serum TOS (s-TOS) was associated with UI after age-adjustment. Follicular fluid OSI (FF-OSI) was negatively associated with embryo quality and embryo score in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI was observed on implantation, clinical pregnancy, and live birth rate. What are the implications of these findings for clinical practice and/or further research? Evaluation of FF-OSI in women with unexplained infertility can be considered to predict embryo quality. Further studies that evaluate antioxidant agents to decrease oxidative stress in UI and its' clinical implications are warranted. [ABSTRACT FROM AUTHOR]

The present retrospective cohort study analysed data of couples with unexplained infertility who underwent two to three intrauterine insemination (IUI) cycles. The inclusion criteria were age 20-40 years, failure to conceive for at least two years of unprotected intercourse, ovulation, normal semen analysis, and tubal patency. Total of 578 IUI cycles of 286 couples with unexplained infertility were included in the final analyses. The mean age and duration of infertility of the study population were 28.8 ± 5.1 and 5.2 ± 3.4 years, respectively. The clinical pregnancy rate (CPR) and live birth rate (LBR) per cycle were 16.6 and 13.1%, respectively. The cumulative CPR following two to three IUI cycles was 33.5% and the cumulative LBR was 26.5% for the entire cohort. The duration of infertility was significantly shorter in women whose IUI attempt were successful (p = .036). Up to three cycles of IUI with ovarian stimulation seems as an effective first-line treatment modality in unexplained infertility.IMPACT STATEMENTWhat is already known on this subject? Cont rolled ovarian stimulation combined with intrauterine insemination (IUI) is a common infertility treatment as a low-cost, less-invasive alternative to in vitro fertilisation (IVF) and was approved as a first line treatment option for unexplained infertility However, the UK National Institute for Health and Care Excellence (NICE) guideline states that IUI is not recommended to couples with unexplained infertility, male factor and mild endometriosis, unless the couples have religious, cultural or social objections to proceed with IVF.What do the results of this study add? Up to three IUI cycles with ovarian stimulation can be considered as an effective treatment modality in unexplained infertility even in couples who could not achieve pregnancy by expectant management for two years.What are the implications of these findings for clinical practice and/or further research? The clinicians should reconsider the NICE recommendation of IVF in the light of recent studies including ours which recommend IUI together when dealing couples with unexplained infertility. [ABSTRACT FROM AUTHOR]

To investigate the anxiety levels among infertile women and their partners also factors that may affect the anxiety status A total of 403 infertile couples who applied to Infertility Outpatient Clinics of a University-affiliated Teaching and Research Hospital were included in the study. The infertile group was divided into two groups as primary and secondary infertile. One hundred and thirty-two fertile couples who applied to Gynecology Outpatient Clinics composed the control group. Hamilton Anxiety Rating Scale (HAM-A) form was filled by the infertile couples to evaluate the anxiety status before they started their treatment. Three hundred and twenty infertile and 84 fertile couples completed the study. The mean total scores of HAM-A of women were similar between the groups. So were the scores of their husbands. In all groups, women had significantly higher mean total HAM-A scores than their husbands. There was no association between the mean HAM-A score of women and age, BMI, AFC, duration of marriage, duration of infertility, number of previous treatment cycles. Education status, working status and family structure of women did not correlate with the mean HAM-A score. Unexplained primary and secondary infertile couples had similar anxiety scores before the commencement of fertility treatments. However, the scores were higher in women than their male partners. Since the burden of treatment and the likelihood of treatment failure might increase the level of anxiety the women could be offered proper cognitive coping and relaxation interventions. [ABSTRACT FROM AUTHOR]

: To examine the effect of paternal age on intracytoplasmic sperm injection (ICSI) outcomes in unexplained infertility : This retrospective study, done at the Hamad Medical Corporation, Doha, Qatar screened infertile couples who underwent ICSI between 2014 and 2019 for the inclusion and exclusion criteria defining 'unexplained infertility'. Couples recruited were allocated into two groups: Group A (paternal age <35 years) and Group B (paternal age ≥35 years). Baseline characteristics, investigations including semen and advanced sperm function tests and ICSI records were compared for primary outcomes such as fertilisation, cleavage, clinical pregnancy, miscarriage and live birth; and secondary outcomes such as semen parameters and advanced sperm functions (DNA fragmentation index and oxidation reduction potential). : We found that final pregnancy outcomes including clinical pregnancy rate (P = 0.231), live-birth rate (P = 0.143), and miscarriage rates (P = 0.466) were not significantly different between the two age groups. Normal fertilisation (P = 0.01) and cleavage rate after ICSI (P = 0.001) were statistically significant when the age groups were compared. Also, normal sperm morphology was found to be significantly different (P = 0.041). : Advanced paternal age affects sperm morphology, fertilisation and embryo cleavage in ICSI but does not appear to affect clinical pregnancy, miscarriage or live-birth rates. ICSI appears to be a valid fertility treatment option in advancing paternal age. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the structural features of the endometrial tissues, the immunohistochemical expression of MUC-1, which plays an important role in implantation, and the biochemical markers during the implantation window. Randomly chosen 18 fertile and 18 unexplained infertile women that have 27–32 days long menstrual cycle, normal hormonal values, normal USG findings of ovary and endometrium were included. Five, six, and seven days after ovulation, endometrial biopsies were taken and prepared in accordance with light and electron microscopy tissue preparation methods. Immunohistochemical methods were used to determine MUC-1 expression in the tissues. Serum hormone levels were determined. The MUC-1 immunoreactivity, as well as the serum levels of FSH, LH, TSH, estrogen, progesterone, and total testosterone did not differ significantly between the two groups; however, prolactin levels were higher in the infertile group. In the unexplained infertile samples, intraepithelial lymphocytes were frequently observed, the microvilli of the surface columnar epithelium were widespread, cells with pinopodes as well as vesiculated cells were minimal, pinopode development was insufficient, and the development of the endometrial glands was deficient. It was concluded that these structural differences observed in the surface and glandular epithelium of the endometrium in unexplained infertile patients may be due to the insufficiency of these cells in responding to steroid hormones; therefore, these changes may affect the implantation of the blastocyst in the endometrium. [ABSTRACT FROM AUTHOR]

When considering empirical medical management (EMT) options for men with unexplained infertility (UI), clomiphene citrate (CC) has been shown to positively influence sperm parameters in hypogonadal men. Unfortunately, the optimal cut point for defining hypogonadism for this patient population has not been established. We hypothesized that hypogonadal men with UI having the lowest serum total testosterone (TT) (<265 ng/dL) would have a significant post-CC improvement in both TT and semen characteristics compared to those in the TT > 264 ng/dL group. We performed our study based on an IRB-approved retrospective chart review of 83 males with UI receiving more than 90 days of 50 mg daily CC. Serum TT and semen characteristics were studied in 83 patients before and in 23 patients after CC treatment. Median TT level increased from 256 ng/dL to 630 ng/dL (p < 0.001, n = 83) and SC increased from 6 ( 10 6 /ml) to 20 ( 10 6 /ml) (p < 0.016, n = 23). Overall, our results demonstrated the following: (1) CC treatment at all currently used serum TT cut-points resulted in significant improvement in both TT (p < 0.001) and sperm concentration (p = 0.03). No significant change in post-CC sperm motility or morphology was noted. (2) Correlation and linear regression analyses demonstrated that CC treatment significantly increased TT in 96% (22 of 23) of patients, and (3) when grouped as two cohorts (≤264 and >264 ng/dL), sperm concentration and TT improved 2.3 to 2.6-fold (p < 0.001) and 1.45 to 2.5-fold (p < 0.01) respectively. Thus, for hypogonadal men with UI, CC significantly improved TT and sperm concentration regardless of pre-treatment, baseline serum TT level. For this reason, CC treatment should be considered in men with UI having a TT < 400 ng/dL. [ABSTRACT FROM AUTHOR]

This study aimed to assess the endometrial receptivity during implantation window in women with unexplained infertility. A prospective study recruited 168 women with unexplained infertility and 169 fertile women. Ultrasonic parameters and biomarkers in the uterine fluid were detected. The endometrial vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were significantly higher in fertile women as compared with unexplained infertile women, and the integrin αvβ3, vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), and leukemia inhibitory factor (LIF) levels in uterine fluid were significantly higher in fertile women. The biochemical pregnancy rate, clinical pregnancy rate, and ongoing pregnancy rate in fertile women were 20.12%, 18.34%, and 17.75%, respectively, which were significantly higher compared with unexplained infertile women (7.14%, 5.36%, and 4.17%, respectively). Endometrial thickness (ET), endometrial volume (EV), VI, FI, and VFI measured by ultrasound, and the integrin αvβ3, VEGF, TNF-α, and LIF levels in uterine fluid were all significantly higher in pregnant women as compared with nonpregnant women. The best parameters of ultrasonic indicators for predicting endometrial receptivity in women with unexplained infertility were FI(AUC = 0.894, sensitivity 93.8%, and specificity 83.1%). Integrin αvβ3 had the best predictive value for endometrial receptivity among biomarkers in the uterine fluid (AUC = 0.921, sensitivity 96.7%, and specificity 89.5%). Women with unexplained infertility present declined endometrial receptivity. Endometrial ultrasonic parameters detected by three-dimensional power Doppler and biomarkers in the uterine fluid may be effective indicators to predict endometrial receptivity. [ABSTRACT FROM AUTHOR]

The prevalence of infertility is increasing and worrisome. About 10 to 30% of infertility is classified as idiopathic or unexplained infertility (UI).TGF-β is multifunctional and immunoregulatry cytokine which regulates both implantation and adhesion of trophoblasts to the extracellular matrix during pregnancy. The aim of the current study was to investigate the association between two polymorphisms rs1800470 (C29T) and rs1800471 (G74C) of the TGF-β1 gene in Iranian patients with unexplained infertility. A total of 250 UI patients and 484 healthy individuals with no history of infertility were included in the study. The amplification and sequencing of target DNA fragments were done using PCR and automated sequencing methods, respectively. The effects of these polymorphisms on both TGF-β1 structure and function of mRNA and protein were analyzed using new in-silico tools. The frequency distribution of the alleles, genotypes, and haplotypes of both rs1800470 and rs1800471 polymorphisms had a statistically significant difference between subjects and controls. CC genotype of TGF-β1 rs1800470 (29C→T) increase the risk of UI in male UI patients. Moreover, C alleles of TGF-β1 rs1800471 was associated with increased risk of UI in female UI patients. Couples, subgroup analysis revealed a significant association between TGF-β1 polymorphisms (rs1800470, rs1800471) and the risk of UI in male, female, and all UI patients. The frequency of TG and CG haplotypes were statistically different in both UI and healthy subjects group (P < 0.05). RS1800471 polymorphisms changed the secondary structure of TGF-β1 mRNA and resulted in the removal of one mRNA arm and creation of two new arms. Taken together, the results of the current study suggest that TGF-β1 functional polymorphisms may play an important role in the susceptibility to UI in Iranian population. According to in silico analysis, polymorphisms in TGF-β1 can reduce mRNA half-life and, therefore, reduced TGF-β1 expression. [ABSTRACT FROM AUTHOR]

It has been realised that rhythmic peristalsis of the ostia and tubes can be observed during hysteroscopy. The aim of this study was to examine the presence of tubal peristaltic dysfunction in unexplained infertility (UI). Hysteroscopy was performed in 35 women with UI and in 37 healthy fertile women. Bilateral tubal peristalses were assessed hysteroscopically by the observation of methylene blue injection and its transport to the Fallopian tubes. Tubal patency was evaluated with laparoscopic chromopertubation. Two women in control group (6.67%) and eight women in UI group (30.77%) had no tubal peristalsis, at least one tube with normal tubal patency. The difference was statistically significant (p = .019). Tubal peristaltic dysfunction may be a hidden cause of subfertility in women with bilateral patent Fallopian tubes. There is a definite need for larger trials to identify tubal peristaltic dysfunction as a cause of UI. Impact statement What is already known on this subject? Unexplained infertility has no identified pathophysiologic basis. It has been realised that rhythmic peristalsis of the ostia and tubes can be observed during hysteroscopy. What do the results of this study add? Tubal peristaltic dysfunction was detected in two tubes (3.70%) in a control group and nine tubes (19.57%) in women with unexplained infertility, when the tubes were patent. The difference was statistically significant (p = .012). What are the implications of these findings for clinical practice and/or further research? In cases of bilateral patent Fallopian tubes such as in unexplained infertility, tubal peristaltic dysfunction may be a hidden additional cause of subfertility. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of nitric oxide donor’s treatment on the pregnancy rate and uterine blood flow in patients with unexplained infertility undergoing clomiphene citrate stimulation and intrauterine insemination. A total of 120 patients were randomly allocated to a control group who received 100 mg clomiphene citrate daily from day 5 to 9 of cycle plus placebo vaginal tablets, and a study group received clomiphene citrate plus isosorbide mononitrate 10 mg vaginal tablets. Vaginal ultrasound was done before treatment and every other day starting from day 12 of cycle to count mature follicles and ovulation was triggered by IM injection of 10 000 IU hCG when one follicle measured 18 ≥ mm followed by intrauterine insemination after 36 h. The endometrial thickness, uterine arteries resistance and pulsation indices, and endometrial vascular flow and vascular flow indices were measured before treatment and at day of hCG injection. Results were analyzed after one cycle treatment using the Mean ± SD, the Studentttest and the Fisher Exact test. Significant result was considered atpvalues <0.05. The study group had significant higher pregnancy rate/cycle, higher endometrial and lower uterine artery blood flow indices (p < 0.05). [ABSTRACT FROM PUBLISHER]

The purpose of this study is to analyse the effect of luteal-phase support on pregnancy rates in gonadotropin + intra-uterine insemination (Gn/IUI) and clomiphene citrate (CC) +IUI (CC/IUI) cycles in patients with unexplained infertility. Equal numbers of patients were recruited in two treatment arms (CC/IUI and Gn/IUI) (n = 100, n = 100, respectively). In each group, 50 patients received vaginal progesterone for 14 days (Crinone 8% vaginal gel, 90 mg per day) for luteal-phase support from the day after IUI and continued until menstruation or the 10th week of gestation if pregnant. There were 29 clinical pregnancies among 200 patients. Pregnancy rates were 12% in CC/IUI cycles, 10% in luteal-phase-supported CC/IUI cycles 16% in Gn/IUI cycles and 20% in luteal-phase-supported Gn/IUI cycles. Although pregnancy rates were higher in Gn/IUI cycles compared to CC/IUI cycles, luteal-phase support did not significantly affect the pregnancy rates in both groups. This study implies that luteal-phase support with progesterone has no pronounced beneficial effect on pregnancy rates in either CC/IUI or Gn/IUI cycles in patients with unexplained infertility. [ABSTRACT FROM AUTHOR]

We aimed to compare ovarian (O), uterine (U) and spiral (S) artery (A) resistance of patients diagnosed as fertile, unexplained infertility (UI) and tubal factor infertility (TFI) in the peri-implantation period and independent from the impact of the treatment. UI (n = 70), TFI (n = 75) and fertile (n = 72) patients' ovarian, uterine and spiral artery pulsatility index (PI), resistance index (RI) and the endometrial thickness, serum estradiol and progesterone levels were compared. The specificity and sensitivity values were calculated according to determined cutoff values. Both TFI and control groups' UA PI values were significantly lower than the UI group's PI values. The highest UA RI values were found in UI group and the lowest values were in the control group. UI and TFI groups' OA PI/RI values were significantly higher than the control group. Both the control and TFI groups' SA PI/RI values were significantly lower than UI group's PI/RI values. UI patients' uterine and spiral arteries PI values >1.86 and >0.85, RI values >0.80 and >0.53 can be used as a valuable test showing reduced uterine perfusion. Ovarian artery PI values >0.96 and RI values >0.58 can be used as tests showing decreased ovarian perfusion in patients with TFI. In these patients, embryo cryopreservation can be considered. [ABSTRACT FROM AUTHOR]

The recent National Institute for Health and Care Excellence (NICE) guideline on Fertility (2012) suggests that IVF should be offered to couples with unexplained subfertility after 2 years of expectant management. The evidence on which these recommendations are based is not robust and there is a lack of agreement among specialists regarding the management of unexplained subfertility. We conducted an online survey among fertility specialists to find out the general consensus regarding the management of these couples. An e-mail questionnaire was sent to 420 reproductive medicine clinicians and 136 (32.38%) replied. Only 16% said they would always recommend IVF as the first line management for these couples, irrespective of age and duration of infertility. Of those surveyed, 39% agreed to the new NICE proposal, 33% agreed partly and 25% did not agree at all. A total of 27% of the respondents said they would definitely change their practice according to the NICE proposal but 30% said they would not; 29% said they might change their policy while the rest were unsure. This survey confirms the ongoing clinical uncertainty among fertility specialists in managing couples with unexplained subfertility. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of empiric use of luteal phase progesterone supplementation to improve endometrial receptivity in women undergoing treatment with clomiphene citrate in combination with intrauterine insemination (CC-IUI). Design: Retrospective cohort analysis. Setting: University fertility center. Patients: 426 CC-IUI cycles from 292 patients with unexplained infertility. Interventions: Patients were treated with micronized intravaginal progesterone 100 mg twice daily beginning approximately three days after CC-IUI. Main outcome measure(s): Clinical pregnancy per initiated cycle as defined by presence of fetal heart rate on ultrasound. Results: Clinical pregnancy rate was higher in patients receiving luteal phase support compared to patients not receiving luteal phase support (odds ratio: 2.04; 95% confidence interval: 1.01-4.14) after adjusting for all factors in the analysis using a multivariate logistic regression model. Age at the start of the cycle, BMI and CC dose were not shown to have an effect on clinical pregnancy rates. Patients with endometrial lining (EML) thickness 6-8 mm and >8 mm had increased clinical pregnancy rates compared to EML <6 mm independent of luteal phase progesterone use. Patients who appear to receive the greatest benefit of progesterone supplementation are in the 6-8 mm EML cohort. Conclusions: Luteal phase progesterone supplementation in CC-IUI cycles can improve endometrial receptivity as judged by the improved clinical pregnancy rates as the primary outcome. [ABSTRACT FROM AUTHOR]

SPRASA (also referred to as SLLP1) is a protein identified in the acrosome of human sperm and encoded by the gene SPACA3. SPRASA is associated with sperm-oocyte recognition and binding, and may play a role in fertility. In order to determine whether variants in the SPACA3 gene are associated with human infertility, we undertook a genetic analysis of 102 infertile and 104 fertile couples. Three gene variants were identified using PCR-based DNA sequencing; 1) an insertion of TGC within a quadruple tri-nucleotide (TGC) repeat region in the 5' untranslated region (UTR) (g.-22TGC(4_5), 2) a guanine to adenosine transition at position 239 (c.239G> A) resulting in a non-synonymous amino acid substitution from cysteine to tyrosine (p.C80Y) at position 80 in the putative transmembrane region, and 3) a novel nucleotide variant (c.691G> C) located in the 3'UTR. A functional effect of the g.-22TGC (4_5) was confirmed by a luciferase expression assay, while the effects of the variants c.239G> A and c.691G> C were predicted using in silico analysis. Although the frequencies of these variants were not significantly different between the infertile and fertile populations, we present evidence that the variants could affect the expression levels or function of SPRASA, thereby affecting a couple's fertility. Larger populations, especially individuals/couples with unexplained infertility, need to be screened for these variants to validate a relationship with fertility. [ABSTRACT FROM AUTHOR]

Adrenomedullin (AM) and its receptor subunit, calcitonin receptor-like receptor (CLR) are known to be important for endothelial function. The genotypes and phenotypes of AM and CLR in the endometrium were studied in relation to unexplained infertility. Endometrial biopsies from 12 fertile and 11 infertile women and blood samples from 156 fertile and 106 infertile women were collected. Protein and mRNA expression of AM and CLR was determined using immunohistochemistry and real time PCR. Allele and genotype frequencies in the AM (rs4399321 and rs7944706) and CLR genes (rs696574, rs1528233 and rs3771073) were performed using Taqman genotyping assays. Unexplained infertility was characterised by lower number of vessels stained with CLR in endometrium compared to fertile controls. There was no difference in AM expression. This could not be explained by SNP analysis in the AM or CLR genes. Imbalance in the AM/CLR system might alter endothelial function in women with unexplained infertility. [ABSTRACT FROM AUTHOR]

This study aimed at evaluating the role of laparoscopy in the management of unexplained infertility in a prospective randomised controlled trial. The study comprised of 255 patients as a study group and 257 patients as a control group. All women had unexplained infertility. Patients in the study group had laparoscopy followed by ovarian stimulation and timed intercourse for six cycles, while patients in the control group were treated directly with ovarian stimulation and timed intercourse for six cycles. Severe adhesions were found in one in each of the two groups, respectively. They were referred directly to the IVF/ICSI programme. Moderate pelvic endometriosis was demonstrated in three cases in the two groups. Again, severe endometriosis was found in two cases in the study groups and they were referred to the IVF/ICSI programme. After 6 months of follow-up, clinical pregnancy occurred in 114/255 (44.7%) in the study group and 107/257 (41.7%) in the control group and the difference was not statistically significant (p > 0.05). The miscarriage rate was similar in the two groups. We concluded that laparoscopy could be postponed when proceeding in the management of unexplained infertility, until ovarian stimulation and timed intercourse had been found to be unsuccessful in achieving pregnancy. [ABSTRACT FROM AUTHOR]

Purpose. To compare the efficacy of lyophilised urinary hMG (HP-hMG) with recombinant FSH (rFSH) in women with unexplained infertilıty undergoing a controlled ovarian hyperstimulation with intrauterine insemination (IUI). Methods. Forty-nine consecutively seen women with unexplained infertility were randomised to a controlled ovarian hyperstimulation with IUI cycle either with rFSH or HP-hMG. The outcome was compared by independent samples t-test. Results. The mean patient age and duration of infertility were not different (29.5 ± 5.7 and 4.9 ± 2.7 years in rFSH; 28.8 ± 3.2 and 6 ± 4.2 in HP-hMG group) ( p = 0.6 and p = 0.2). The mean body mass index (BMI) and basal hormones were similar. Total dose of gonadotropin used (710 ± 236 vs. 636 ± 185 IU) and duration of the cycles (9 ± 2.1 vs. 8.3 ± 2.3 days) showed no significant difference ( p = 0.2). Number of follicles, serum oestradiol (E2), and the endometrial thickness on the day of hCG were comparable. Two singletons in each group were obtained. Conclusions. These data suggest that HP-hMG and rFSH may be equally suitable in mild ovarian stimulation for unexplained infertilıty. Further data derived from larger study population are needed to determine whether higher amounts of two gonadotropins in this subgroup might produce any benefits or unfavourable effects. [ABSTRACT FROM AUTHOR]

Vaginal progesterone (P) has been suggested to be used for luteal phase support (LPS) in controlled ovarian stimulation (COH)–intrauterine insemination (IUI) cycles, however, no concensus exists about the best P dose. Therefore, considering the fecundability rate as the primary end point, our main objective was to find the optimal dose of P in COH–IUI cycles, comparing the two groups of women, each of which comprised of 100 women either on 300 mg or 600 mg of intravaginal P tablets, in a prospective randomized study design. The mean age of the women, duration of infertility, basal and day of hCG injection hormone levels in the female and sperm parameters were similar in the two study groups. Also, duration and dose of gonadotropin given, number of follicles, endometrial thickness, the total, ongoing and multiple pregnancy rates were comparable in both groups. We, therefore, claim that 300 mg of intravaginal micronized P should be the maximum dose of LPS in IUI cycles. [ABSTRACT FROM AUTHOR]

It has been suggested that approximately 10% of females demonstrate premature ovarian aging. In younger women the diagnosis is frequently overlooked, since ovarian function parameters often still lie within ranges that are traditionally considered normal. Age-specific ovarian testing normalizes ovarian function parameters according to age. Such testing can, therefore, detect subtle ovarian abnormalities at earlier stages. Timely diagnosis of premature ovarian aging mandates the understanding of age-specific ovarian function testing. Among active infertility patients such testing reveals a far higher prevalence of premature ovarian aging risk than in a general population, the highest in youngest patients and a declining risk as women age. Since patient populations at different fertility centers vary in severity of ovarian compromise, center-based, age-specific ovarian function tests are not universally applicable. Such universally applicable function tests can only be defined in normal, fertile populations and their establishment should become a priority for the profession. [ABSTRACT FROM AUTHOR]

Issues relevant to the current management of female infertility include the aging female infertile population and the obesity epidemic. Diagnosis is straightforward when causes are severe and laparoscopy is still the preferred method for assessing for tubal factor infertility and endometriosis. Laparoscopy can be timed to take advantage of the spontaneous pregnancy rate that exists mainly in unexplained infertility. IVF remains the dominant treatment, although traditional measures still have a major role. Internationally, IVF opportunities are limited in view of cost. The New Zealand system offers a prioritization system that enables public access to IVF for couples most in need and for those most likely to benefit. [ABSTRACT FROM AUTHOR]

Despite improvements in both diagnostic assessment and treatment of infertile couples, many couples still have no explanation for their infertility. Unexplained infertility (the failure to conceive of a couple in whom no definitive cause for infertility can be found) has an incidence of 10-20% in all infertile couples. The incidence varies with the population studied and with the criteria used. Unexplained infertility is not an absolute condition but rather a relative inability to conceive, and many of these couples may conceive without treatment. The treatment options for unexplained infertility are several and the treatment results are promising. Expectant management can be recommended if the woman is under 28-30 years of age and the infertility duration is less than 2-3 years. In vitro fertilization (IVF) has revolutionized the treatment of infertile couples, as well as profoundly increasing the basic understanding of human reproduction. IVF can be used as both a diagnostic and a therapeutic tool in couples with unexplained infertility. The pregnancy rates with IVF are good, at 40% per treatment cycle. In addition, the outcome of pregnancies among women with unexplained infertility is generally comparable to that of spontaneous and other pregnancies using assisted reproductive technologies. [ABSTRACT FROM AUTHOR]