Cause Of Unexplained Infertility Research Articles

The prevalence of antiphospholipid antibodies and effects on the outcomes of in vitro fertilization

Introduction: The problem of infertility is common worldwide. IVF remains the most widely used technique of assisted reproductive technology. Embryo implantation failure is a common cause of unexplained infertility and recurrent miscarriages, thus the relationship between antiphospholipid antibodies and embryo implantation failure after IVF and embryo transfer is an important problem in fertility medicine that must be studied. Patients and methods: A retrospective and prospective (bidirectional) cohort study were conducted at the Laboratory Department of the Faculty of Medicine, and Hospital from June 2017 to June 2021. The sample size was 1000 participants, 900 of them were retrospective (2017–2020), and 100 were prospective (2020–2021). Data was collected, including patients’ demographics, type and duration of fertility, and antiphospholipid antibody values. Inclusion criteria-Women <40 years old, undergoing IVF, and in the retrospective study, patients who undergo IVF and who have antibody data, positivity of phospholipids, and/or anticardiolipin, and/or B2 glycoprotein I, and the presence of the gestational sac on ultrasound as a criterion for pregnancy. We performed a PTT LA for the control group in a cohort study (20 healthy women), then a PTT LA test, and the blending test were performed, and the values were considered positive if the correction was not made. The PTT LA test is a screening test. Results: The average age of the women was 31.91, the success rate of assisted fertilization in inducing pregnancy in the last trial was 52.8%, the prevalence was 4.4% of anticardiolipin IgG, 2.6% of anticardiolipin IgM, and 4% of Lupus anticoagulant. No relation was found between the antiphospholipid value and the age of the women, the number of times the experiment was conducted, the rate of success and failure, the type of infertility, and the number of oocytes induction, while the duration of sterility was affected by positive values of IgG and lupus coagulant antibodies. Conclusion: There is no need for a routine antiphospholipid assay for female candidates for IVF, and when it is confirmed, treatment is required by Anticoagulants.

What Medically Assisted Reproduction Should Be Offered in Unexplained Infertility?

Conflict of Interest: BWM is supported by a NHMRC Investigatorgrant (GNT1176437). BWM reports consultancy and travel support from Merck, Guerbet and Organon and research funding from Merck. In up to half of all couples who seek medical assistance for infertility a direct cause for their inability to conceive cannot be identified and they are therefore labelled as having unexplained infertility. Unexplained infertility is characterized by normal ovulation, tubal patency, and a normal (or slightly deviant) semen analysis in the male partner according to WHO-criteria. The causes of unexplained infertility remain, as determined by its definition, largely unknown. Available treatments for unexplained infertility include intrauterine insemination (IUI) with ovarian hyperstimulation, in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), but also tubal flushing or lifestyle interventions. Treatments like IUI and IVF might on one hand be effective because they increase the number of possible conceptions, for example by creating multiple follicles or embryos, but they also might overcome an unknown barrier for conception. Since, in couples labelled with unexplained infertility natural conception by definition never can be excluded, the prognostic profile of couples for such natural conception is instrumental. I will argue that understanding of prognosis for natural conception should be one of the cornerstones for the management of infertility. If the prognosis for a ‘spontaneous pregnancy’ within a reasonable time frame is high enough, it might be justified to delay treatment in these couples for some time. After that, IUI should be the treatment of first choice.

Therapeutic potential of testosterone on sperm parameters and chromatin status in fresh and thawed normo and asthenozoospermic samples

BackgroundHormonal changes alter the physiological level of ROS and cause oxidative stress in the cell. As estimated, hormonal deficiencies, environmental and ideological factors make up about 25% of male infertility. Pathogenic reactive oxygen species (ROS) is a chief cause of unexplained infertility. Limited studies exist on the effects of testosterone on human sperm culture. Therefore, in the current study, the effect of different doses of testosterone on sperm parameters and chromatin quality was investigated. Materials and methodsSemen samples from 15 normospermic and 15 asthenospermic patients were prepared by swim up method, and then were divided into four groups by exposing to different concentrations of testosterone (1, 10, and 100nM) for 45min. Samples without any intervention were considered as control group. All samples were washed twice. Sperm parameters and chromatin protamination were assessed in each group and the remains were frozen. After two weeks, all tests were repeated for sperm thawed. Also, the MSOM technique was used to determine the sperm morphology of class 1. ResultsAlthough sperm parameters were not show any significant differences in normospermic and asthenospermic samples exposed to different concentrations of testosterone before and after freezing, chromatin protamination was significantly decreased in the normospermic samples exposed to 10nM of testosterone before freezing (p<0.006), as well as 1 and 10nM of testosterone after freezing compared to control samples (p=0.001 and p=0.0009, respectively). Similarly, chromatin protamination in the asthenospermic samples was significantly decreased at concentration of 1nM of testosterone before and after freezing (p=0.0014 and p=0.0004, respectively), and at concentration of 10nM of testosterone before and after freezing (p=0.0009, p=0.0007) compared to control samples. ConclusionUsing a low dose of testosterone in the sperm culture medium, has positive effects on chromatin quality.

Molecular and Ultrastructure Studies on Human Sperms in cases of Unexplained Infertility Undergoing Intracytoplasmic Sperm Injection (ICSI)

Infertility is a global health problem, affects 25% of couples. It is described as the incapacity of a couple to conceive a child after 12 months of continued sexual intercourse. Unexplained infertility is described and diagnosed as the patients’ semen analysis is within normal values and the patient’ partner examinations revealed no causes of infertility. The study aimed to find out the causes of unexplained infertility in men using ICSI. This was done through evaluation of the oxidative stress (OS) parameters, semen, molecular analysis (Caspase-3 activity and DNA integrity), detecting the immunological antisperm antibody (ASA) in semen samples; in addition to the ultrastructural evaluations of spermatozoa using TEM examination. Regarding to OS analysis, the results showed significant increases in the concentrations of MDA in the seminal fluids of patients, while SOD and GSH activities revealed significant decreases, comparing to the control value. Catalase contents showed no significant differences. Cspase-3, DNA integrity (genetic diversity) as well as Antisperm antibody (ASA) analysis revealed significant increases in samples of unexplained ferirtility patients, compairing to the control. The electron micrographs showed the appearance of head and tail abnormalities, where there were marked deformities in size of head region, loss of chromatin contents and an appearance of intranuclear cytoplasmic retention (INCR). The axoneme showed incomplete number of microtubules and marked loss of the central axonemal doublets; in addition to the dysplasia and disorganization of the mitochondrial and the the fibrous sheath.

A comparison between uterine artery blood flow in fertile and unexplained infertile women by Doppler ultrasound using pulsatility index and resistance index

Background and objectives: Infertility is inability to conceive after one year of regular unprotected intercourse. Unexplained infertility is present if the basic fertility investigations are normal. The objective of this study is to investigate the use of uterine artery blood flow as a cause of unexplained infertility (using pulsatility index, resistance index) and compare them to fertile women. Methods: A prospective cohort study was performed on 70 patients (35 fertile and 35 with unexplained infertility patients) in Sulaymaniyah Maternity Teaching Hospital, Kurdistan Region, Iraq, during October 2016 to December 2017. Transvaginal color Doppler ultrasound was done in the mid luteal phase (day 21 - 24) for uterine artery by using pulsatility index and resistance index. Results: The age of the patients ranged from 20 - 39 years. The uterine artery pulsatility index was significantly higher in the unexplained infertile women (mean ± SD = 2.78 ± 0.615) than fertile women (mean ± SD = 2.42 ± 0.325). The uterine artery blood flow resistance index was significantly higher in unexplained infertile group (mean ± SD = 0.899 ± 0.066) than fertile women (mean ± SD = 0.83 ± 0.054). Conclusions: Unexplained infertility is associated with decreased uterine artery blood flow and increase uterine artery resistance (pulsatility index and resistance index) when compared with fertile women.

Can we accurately diagnose endometriosis without a diagnostic laparoscopy?

Endometriosis is a progressive, estrogen-dependent, chronic inflammatory disease that affects approximately 6-10% of reproductive age women. Patients usually presents with symptoms, such as non-menstrual pelvic and abdominal pain, ovulatory pain, dyspareunia, dysmenorrhea, dyschezia, and/or changes to bowel or bladder function, which can be exacerbated during ovulation or menses. Endometriosis is a leading cause of unexplained infertility, accounting for up to 50-80% of cases. Currently, altered endometrial receptivity and progesterone resistance are some of the leading theories that could explain endometriosis-related implantation failure. In the endometrium, the B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL-6) protein forms a complex that binds to and inactivates regulators of the progesterone pathway, leading to progesterone resistance, aberrant decidualization, implantation failure, and recurrent miscarriages in women diagnosed with endometriosis. Surgical diagnosis consisting of laparoscopy, with or without histologic confirmation, is still considered the gold standard for diagnosis of endometriosis. Development of noninvasive screening and diagnostic tests to accurately identify patients with endometriosis has become increasing popular. A screening test for endometriosis has been developed to detect endometrial BCL-6 overexpression in asymptomatic women with unexplained infertility or recurrent pregnancy loss. Positive endometrial BCL-6 testing has been associated with recurrent miscarriages and poor in vitro fertilization outcomes. When the underlying cause of endometrial inflammation secondary to endometriosis was treated, an improvement in subsequent live birth rates was seen. Endometrial BCL-6 testing has a high positive predictive value that could help physicians and patients undergoing infertility treatment to seek surgical evaluation for endometriosis, to improve their reproductive outcomes.

LOW PERCENTAGE MOTILITY WHEN SPERM CONCENTRATION IS NORMAL DOES NOT APPEAR TO BE A CAUSE OF UNEXPLAINED FAILURE TO HAVE A LIVE DELIVERY DESPITE IN VITRO FERTILIZATION (IVF)

Some data suggest that sperm with very low motile density can lead to a trend for a lower chance of a live delivery following in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) even despite the transfer of embryos with apparent normal morphology. The purpose of the present study was to see if low % motility in the presence of normal sperm concentration can also be a subtle cause of unexplained infertility. Couples were identified who were sharing donor oocytes when both male partners had normal concentrations of their sperm (≥20x106/mL) but where one had motility <30% and the other ≥50%. Subsequent fertilization rates, embryo quality, as evidence by number of blastomeres on day 3 transfer, and pregnancy rates were determined. ICSI was used or not according to the discretion of the physician. Tabled 1Pregnancy rates based on % motility for shared oocyte cycles when sperm concentration ≥20 mill/mLMotility<30%≥50%# cycles3737% fertilized70.5%70.1%% 6-8 cell day 360.6%70.7%% clinical pregnancy/transfer58.3%68.0%% miscarriage/clinical pregnancy live0.0%35.3%% delivered58.3%44.0%% implantation31.3%40.0% Open table in a new tab There were no statistical differences or trends that would suggest that low % motile sperm, despite normal sperm concentration, leads to embryos with a lower chance to achieve a live delivery. With no trends seen at all, the study will not be continued. Based on other studies, there is a suggestion that sperm from men with very low motile density, used for IVF-ET, the embryos formed, though appearing to be morphologically normal, may be the cause of lower live delivered pregnancy rates. This raised the question as to the possibility that sperm with very low MD may be more likely to have chromosome defects. That data was also based on similar evaluation of matched pairs sharing one pool of oocytes, thus ruling out an oocyte factor. It does not seem that low percentage of sperm motility is a subtle cause of unexplained infertility when sperm concentration was normal based on this pilot study.

Glutathione Content and Glutathione Peroxidase Activity of Sperm in Males with Unexplained Infertility

Summary The study aimed to investigate glutathione peroxidase (GPx) activity and glutathione (GSH) levels in the sperm of patients with unexplained infertility. The sperm samples were collected from subjects with normal semen parameters divided into fertile and infertile groups. Sperm analysis was performed according to the 2010 WHO criteria. Measurement of the GPx activity and GSH were performed by enzymatic assay kits. The higher enzymatic activity recorded in spermatozoa and seminal plasma in the infertile group was close to the significant one – p=0.054 for seminal plasma andp= 0.086 for the spermatozoa.GSH levels were higher in the fertile group in the seminal plasma (p=0.045). Defining the causes of unexplained infertility requires the addition of oxidative stress. In patients with unexplained infertility, the level of glutathione is reduced, and the activity of one of the significant enzyme antioxidants GPx is not changed significantly and even shows a tendency to rise.

The Clinical Experience of Prof. Zhang Xiaofeng in the Treatment of Small Follicular, Ovulatory Infertility with Traditional Chinese Medicine

With the popularization of clinical ultrasound technology, small follicular ovulation infertility is gradually being recognized in clinical practice. Low follicle ovulation refers to the phenomenon that the average value of the three diameter lines of the dominant follicle is less than 14mm-18mm under continuous ultrasound monitoring. The dominant follicle ovulates before it develops to maturity, which is a kind of ovulation disorder and one of the leading causes of unexplained infertility, accounting for 25%-30% of the total number of patients with infertility. At present, Western medicine mostly uses ovulation, stimulating drugs to treat this disease. Still, due to the clinical result of "high ovulation but low pregnancy", there are certain obstacles in treatment. The purpose of this article is to discuss Zhang Xiaofeng's understanding of TCM of this disease. The tutor believes that the location of the disease is in the kidney, and the mechanism of the disease is kidney yin deficiency and blood heat. The treatment principle is sequential therapy, nourishing yin and clearing heat, taking into account the protection of the spleen and stomach, and the therapeutic effect is perfect.

SPERM WITH VERY LOW MOTILE DENSITY (MD) MAY BE A CAUSE OF REDUCED CHANCE OF LIVE DELIVERY DESPITE TRANSFER OF NORMAL MORPHOLOGIC EMBRYOS

To determine if a male factor, specifically low MD, can reduce the chance of a live baby despite normal fertilization and the production of embryos with good morphology. Prospective comparison study. To eliminate an oocyte factor as a confounding variable, the study selected pairs of patients sharing donor oocytes. The only couples selected were those where the male partners of 1 couple had a MD below <10x106/mL and the other male partner ≥10x106/mL. The low MD group when evaluating outcome was further divided into very low MD of <5x106/mL and 5-9.9x106/mL. Only cycles where both couples had a fresh embryo transfer (ET) on day 3 were included. Intracytoplasmic sperm injection (ICSI) was used for couples where MD was <10x106/mL unless strict morphology was ≤4% when ICSI was used even with normal MD. There were 242 ETs in low MD groups and 245 in normal MD group.Tabled 1Comparison of in vitro fertilization (IVF) outcome according to MD in pairs sharing oocytesMotile Density (10x106/mL)<55-9.9≥10# transfers14399245% fertilized72.1%70.9%70.9%% 6-8 cell day 357.3%60.2%62.4%% clinical preg./transfer47.6%49.5%56.3%% miscarriage/clinical preg. live20.6%8.2%16.7%% delivered37.8%45.5%46.9%% implantation26.5%26.7%30.9%Chi-square = NS. Power analysis showed one would need to triple the number of subjects to show that the difference in live delivery rates comparing very low MD vs. normal MD was significant. Evaluating a subset with normal morphology using strict criteria, the live delivered pregnancy rate for very low MD was 36.1% (26/72) vs. 48.3% and miscarriage rate was 29.7% vs. 13.3%. Thus, low strict morphology was not a confounding variable. Since both low MD groups had ICSI performed, and the less severe group did as well as the normal MD group, ICSI did not seem to be a confounding variable. There was an average of 1.8 embryos transferred in the very low MD group vs. 1.9 in the normal MD group. Open table in a new tab Chi-square = NS. Power analysis showed one would need to triple the number of subjects to show that the difference in live delivery rates comparing very low MD vs. normal MD was significant. Evaluating a subset with normal morphology using strict criteria, the live delivered pregnancy rate for very low MD was 36.1% (26/72) vs. 48.3% and miscarriage rate was 29.7% vs. 13.3%. Thus, low strict morphology was not a confounding variable. Since both low MD groups had ICSI performed, and the less severe group did as well as the normal MD group, ICSI did not seem to be a confounding variable. There was an average of 1.8 embryos transferred in the very low MD group vs. 1.9 in the normal MD group. Though the differences were not significant, possibly the results could suggest that even using the best quality oocytes, males with very low MD may be responsible for unexplained failure to achieve a live birth even with the transfer of normal quality embryos by morphologic criteria. Since good oocytes can sometimes correct sperm defects, it may be that these differences may be even greater if the oocytes retrieved are of less quality. Thus, in cases of repeated failure to achieve live deliveries in couples where the sperm has very low MD, instead of switching to donor oocytes, one could consider first trying donor sperm. A larger possibly multicenter study is needed to support or refute this suggested cause of unexplained infertility.

SIRTI and cortisol in unexplained infertile females; a cross sectional study, in Karachi Pakistan

ObjectiveTo explore a disparity in anti-oxidants (SIRT1) and pro-oxidants (cortisol) levels as a plausible cause of unexplained infertility in females. MethodologyIt was a cross sectional study in which 342 females with unexplained infertility were recruited from ACIMC outpatient clinic: 135 infertile cases and 207 fertile controls. Biochemical estimation of serum cortisol and SIRT1 was performed using Enzyme Linked Immuno Sorbent Assay. Statistical comparisons were performed using Student-t test and Mann-Whitney U test. Associations between circulating hormone levels and infertility were determined using Spearman's rank correlation. Associations were considered significant where value of p was less than 0.05. ResultsThe stress hormones profile of case and control demonstrated that the antioxidant SIRT1 was significantly lower in infertile females when compared with the fertile (p =< 0.001) while (the oxidant) Cortisol showed a contrast of results with higher values of in infertile females when compared with fertile counterparts (p =< 0.01). There was a strong negative association observed between SIRT1 and cortisol serum level (r = 0.244, p < 0.001). ConclusionChronic stress causes oxidative stress that is depicted by a decrease in antioxidant levels in infertile females.

Seminal plasma and CD4+ T-cell cytokine profiles in the in vitro fertilization success.

Background:Abnormal female immune response is one of the potential causes of unexplained infertility (UI). Seminal plasma (SP) is an important regulator of female immune responses during pregnancy. This study investigated a SP effect on the expression of CD4+ T-cell-related cytokines in a group of UI woman candidates for in vitro fertilization (IVF) and healthy fertile women.Materials and Methods:This was a semi-experimental study that performed on 20 UI couples (ten unsuccessful and ten successful IVF outcomes) and 10 fertile couples as the healthy group. CD4+ T-cells were separated from peripheral blood mononuclear cells of women by magnetic-activated cell sorting technique and incubated with (stimulated condition) or without (unstimulated condition) SP of their husbands. After incubation, real-time polymerase chain reaction method was used to investigate interleukin (IL)-23, IL-17, IL-4, IL-10, transforming growth factor (TGF)-β, and interferon (IFN)-γ gene expression. Mann–Whitney U-test, Kruskal–Wallis test, and Wilcoxon signed-rank test were used for statistical analysis.Results:Baseline TCD4+ mRNA levels of IL-23 (P = 0.03) and TGF-β (P = 0.01) were different between healthy and infertile groups. However, IL-17, IL-4, IFN-γ, and IL-10 were expressed similarly regardless of fertility status. Comparing mRNA expression before and after SP exposure, our results have shown that relative expression of IL-23 significantly increased in successful (P = 0.04) and unsuccessful IVF groups (P = 0.01), whereas IL-10 expression increased only in the IVF failure group (P = 0.01).Conclusion:SP can make a positive effect on IVF outcome through alteration in CD4 + T-cell-related cytokines expression, especially IL-10 and IL-23.

Towards a gamete matching platform: using immunogenetics and artificial intelligence to predict recurrent miscarriage

The degree of Allele sharing of the Human Leukocyte Antigen (HLA) genes has been linked with recurrent miscarriage (RM). However, no clear genetic markers of RM have yet been identified, possibly because of the complexity of interactions between paternal and maternal genes during embryo development. We propose a methodology to analyse HLA haplotypes from couples either with histories of successful pregnancies or RM. This article describes a method of RM genetic-risk calculation. The proposed HLA representation techniques allowed us to create an algorithm (IMMATCH) to retrospectively predict RM with an AUC = 0.71 (p = 0.0035) thanks to high-resolution typing and the use of linear algebra on peptide binding affinity data. The algorithm features an adjustable threshold to increase either sensitivity or specificity, allowing a sensitivity of 86%. Combining immunogenetics with artificial intelligence could create personalised tools to better understand the genetic causes of unexplained infertility and a gamete matching platform that could increase pregnancy success rates.

Do inflammation and hormone parameters have effects on IVF results in patients with unexplained infertility?

Aim: To invastigate the inflammatory process and hormone parameters as a result of underlying cause of unexplained infertility (UI)Metarial and Methods: In total 153 patients with UI who underwent to intracytoplasmic sperm injection (ICSI) were included in the study. The blood hormones levels were obtained on the 2nd or 3rd day of the menstruation. Other blood count examinations were taken on the day of HCG administration. Relationship regarding embryo grade was also investigated.Results: Of those 153 patients, only 42 of them got pregnant. Mean maternal age was 29.08±3.5 and mean duration of the infertility was 8.19±3.1 years, respectively. There was no statistically significant difference between pregnancy rate, embriyo grade, and FSH, progesterone, fT3, fT4, TSH levels (p>0.05). Also no significant difference was found between pregnancy rate, embriyo grade and hemoglobin, hemotocrit, platelet, mean platelet volume, neutrophil, lymphocyte counts, neutrophil lymphocyte ratio and platelet lymphocyte ratio (PLR) (p>0.05). However, a significant difference was found between embriyo grade and estradiol values (p0.05). There was a negative correlation between hematocrit values and the oosit number collected with the number of embryos (p0.05). PLR was found to be 110.9 (63.6 - 313.2) in pregnant women and 110.5 (51.8 - 390) in nonpregnant patients and the correlation between the PRL measured on HCG day and pregnancy rate.was significant (p=0.002). LH median values measured on HCG day were significantly lower in pregnant group (p0.001). Conclusion: We found that inflammation does not affect on IVF result and estradiol levels significantly effects on embriyo quality. Also there was an inverse correlation between hematocrit levels and the number of oocyte- and number of embryos.Keywords: Infertility; blood cell count; inflammation; estrogen.

Deficiency in Sperm-Egg Protein Interaction as a Major Cause of Fertilization Failure.

Complete elucidation of fertilization process at molecular level is one of the unresolved challenges in sexual reproduction studies, and understanding the molecular mechanism is crucial in overcoming difficulties in infertility and unsuccessful in vitro fertilization. Sperm-oocyte interaction is one of the most remarkable events in fertilization process, and deficiency in protein-protein interactions which mediate this interaction is a major cause of unexplained infertility. Due to detection of how the various defects of sperm-oocyte interaction can affect fertilization failure, different experimental methods have been applied. This review summarizes the current understanding of sperm-egg interaction mechanism during fertilization and also accumulates the different types of sperm-egg interaction abnormalities and their association with infertility. Several detection approaches regarding sperm-egg protein interactions and the associated defects are reviewed in this paper.

Progesterone: a little-known role of the well-known hero

Endometrial polyps and chronic endometritis are two most common causes of unexplained infertility in women of reproductive age.The aim of our study was to conduct a comparative analysis of the hormonal homeostasis and the state of the receptor apparatus of the endometrium in women of reproductive age with endometrial polyps and micropolyps.For a research 4 groups of women were chosen: 34 women with endometrial polyps (IA group), 36 patients with endometrial polyps and micropolyps (IB group), 30 women with micropolyps (IІ group) and 30 healthy women (ІІІ group). In all groups of women the content in blood serum for 3–5 day of a menstrual cycle of gonadotropic hormones (follicle-stimulating hormone, luteinizing hormone) and sex steroid hormones (estradiol, prolactin) was studied, for 21 days of a cycle estimated the content of progesterone. Level of an expression of receptors of progesterone and estrogen estimated in endometrium and at endometrial polyps, also in І a cycle phase.The conducted research revealed reliable decrease in level of progesterone at women with endometrial polyps against the background of lack of significant changes in the receptor device. At patients with micropolyps the tendency to a hypoprogesteronemia was also observed, but changes in an expression of steroid receptors it was not also revealed.The authors conclusion is the low concentration of progesterone initiate non-hormonal pathophysiological mechanisms of development of endometrial polyps which should be considered at purpose of antirecurrent therapy.Thus, in case of progesteron deficit perverse mechanisms literally overlap in an attempt to start the process of tumor. Inflammation is an important component of the physiological menstrual cycle, during prolonged hypoprogesteronemia it becomes pathological. It is directly involved in the formation of such a microenvironment for endometrium in which the mechanisms of fibrosis fully realize their potential, cell proliferation and angiogenesis, creating a strong foundation for the subsequent formation and growth of endometrial polyps. To date, it is proved that an imbalance in estrogen-progesterone system actually increases the risk of developing endometrial polyps, but not always through steroid receptors.

Perbandingan hasil stimulasi ovarium dengan kombinasi klomifen sitrat gonadotropin dan klomifen sitrat pada inseminasi intra uteri

Background: Infertile couple with the cause of unexplained infertility and male factor can follow intrauterine insemination (IUI) program as a cheap and easy method for infertility therapy. Ovarian stimulation by combination of clomiphene citrate and gonadotropin and also clomiphene citrate alone was done as a superovulation mode to get higher number of mature follicle to gain higher pregnancy rate. Objective : To compare the amount of mature follicles and endometrial thickness as an outcome of ovarian stimulation between combination drug of clomiphene citrate and gonadotrophin with clomiphene citrate alone.Methods: Observational retrospective cohort. Subject is one cycle intrauterine insemination stimulated either by combination CC gonadotrophin or CC alone, eligible in inclusion criteria and exclusion criteria. Statistic test used was independent t-test, chi-square and logistic regression.Location of study: Infertility Clinic of Permata Hati, dr. Sardjito Hospital, Yogyakarta.Result: A total of 142 cycle from 98 couples followed IUI and stimulated by combination CC gonadotrophin (n=72) or CC alone (n=70). Multiple mature follicle number was different and statistically significant 77% vs 54%, RR 1,433 (IK95% 1,118-1,836), p=0,005, while endometrial thickness &gt; 7mm was more frequent in combination group but not statistically different with percentage 81,9% vs 74,3%, RR 1,103 (CI95% 0,926-1,315), p=0,367.Conclusion: Ovarian stimulation by combination CC gonadotropin resulting of more multiple mature follicle number while good endometrial thickness was more in combination group but not statistically significant.Keywords: ovarian stimulation, clomiphene citrate, gonadotrophin, multifollicular, endometrial thickness

Alteration in endometrial proteins during early- and mid-secretory phases of the cycle in women with unexplained infertility.

BackgroundCompromised receptivity of the endometrium is a major cause of unexplained infertility, implantation failure and subclinical pregnancy loss. In order to investigate the changes in endometrial protein profile as a cause of unexplained infertility, the current study was undertaken to analyze the differentially expressed proteins of endometrium from early-secretory (LH+2) to mid-secretory phase (LH+7), in women with unexplained infertility.Methods2-D gel electrophoresis was performed to analyze the proteomic changes between early- (n = 8) and mid-secretory (n = 8) phase endometrium of women with unexplained infertility. The differentially expressed protein spots were identified by LC-MS analysis and validated by immunoblotting and immuno-histochemical analysis in early- (n = 4) and mid-secretory (n = 4) phase endometrium of infertile women. Validated proteins were also analyzed in early- (n = 4) and mid-secretory (n = 4) phase endometrium of fertile women.ResultsNine proteins were found to be differentially expressed between early- and mid- secretory phases of endometrium of infertile women. The expression of Ras-related protein Rap-1b, Protein disulfide isomerase A3, Apolipoprotein-A1 (Apo-A1), Cofilin-1 and RAN GTP-binding nuclear protein (Ran) were found to be significantly increased, whereas, Tubulin polymerization promoting protein family member 3, Superoxide dismutase [Cu-Zn], Sorcin, and Proteasome subunit alpha type-5 were significantly decreased in mid- secretory phase endometrium of infertile women as compared to early-secretory phase endometrium of infertile women. Validation of 4 proteins viz. Sorcin, Cofilin-1, Apo-A1 and Ran were performed in separate endometrial biopsy samples from infertile women. The up-regulated expression of Sorcin and down-regulated expression of Cofilin-1 and Apolipoprotein-A1, were observed in mid-secretory phase as compared to early-secretory phase in case of fertile women.ConclusionsDe-regulation of the expression of Sorcin, Cofilin-1, Apo-A1 and Ran, during early- to mid-secretory phase may have physiological significance and it may be one of the causes for altered differentiation and/or maturation of endometrium, in women with unexplained infertility.

Value of hysteroscopy in management of unexplained infertility

Abstract Objective To assess the value of hysteroscopy in unexplained infertility. Methods 200 infertile women in whom standard infertility investigations revealed no abnormalities were included in the study between January 2009 and December 2013. All women underwent hysteroscopy for diagnosis and treatment of any uterine lesion which was previously undetected by hysterosalpingography (HSG). Treated women were followed up for one year during which pregnancy rate was determined. As all other causes that contribute to infertility (other than the subtle uterine lesions) were excluded. No other infertility treatment was performed during this period. Results Of the 200 women studied, hysteroscopy revealed abnormalities in 65 (33%) women. Most uterine abnormalities were mild adhesions, small submucous myomas and polyps and their incidence was greater in women aged ≥ 30 years and women with secondary infertility. The overall pregnancy rate in the treated women within one year of follow up was 46%. Conclusion As a cause of unexplained infertility, subtle uterine abnormalities are diagnosed only during hysteroscopy and they are relatively common in infertility women. Although the presence of these abnormalities is not detected by the basic investigations for infertility, their correction seems to be necessary when infertility is desired and other infertility causes are excluded.

Uterine and ovarian arteries blood flow during the mid luteal phase in women with unexplained infertility

Abstract Objective Altered utero-ovarian blood flow has been claimed to be a subtle cause of unexplained infertility. The aim of this study was to compare between the flow velocity indices in the uterine and ovarian arteries during the luteal phase in fertile and unexplained infertility women. Study design Observational, cross section, controlled study done at the departments of Obstetrics and Gynecology, Benha Faculty of Medicine, Egypt, during the period from October 2010 to October 2011. Patients and methods Two groups each of 30 cases and aged 20-25 years were studied. A control group of fertile women who got pregnant within one year of marriage, and a study group of women with unexplained infertility were included. Trans-vaginal pulsed color Doppler ultrasound was done at days 21–23 of the cycle to measure uterine and ovarian arteries resistance and pulsation indices. Outcome measures Mean uterine and ovarian arteries resistance and pulsation indices in both groups and their values in the diagnosis of altered blood flow in unexplained infertility were measured. Results Women with unexplained infertility had significantly higher uterine and ovarian arteries pulsation index ( P Conclusions Unexplained infertility is associated with decreased uterine and ovarian arteries blood flow during the luteal phase. More studies are needed to support this conclusion and to evaluate the possible role of perfusion enhancer drugs in increasing utero-ovarian blood flow and enhancing pregnancy.