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Endometrial pinopode and alphavbeta3 integrin expression is not impaired in infertile patients with endometriosis.

PURPOSE: To investigate endometrial receptivity in terms of pinopode formation and alphavbeta3 integrin expression in infertile women with endometriosis during natural cycles. METHODS: We investigated the expression of alphavbeta3 integrin and pinopode formation in the endometrium of 12 infertile patients with stage I or II endometriosis as the only cause of infertility, 12 infertile patients having unexplained infertility, and 12 fertile women who were undergoing tubal sterilization. Two endometrial biopsies (postovulatory day +7 to +8 and 4 days later) were performed during a single menstrual cycle in each subject. RESULTS: No statistically significant difference regarding alphavbeta3 integrin expression and pinopode formation was found between infertile patients with endometriosis and the two control groups. CONCLUSION: alphavbeta3 integrin expression and pinopode formation are not reduced during the window of implantation in patients with stage I-II endometriosis. Whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with those markers of implantation, warrants further studies.

Adult↗

Increased natural killer-cell activity is associated with infertile women.

PROBLEM: An increase in natural killer (NK)-cell activity has been observed in women with unexplained recurrent miscarriages. Because of the many similarities between infertility and early pregnancy loss patients, we investigated whether infertile women had raised NK-cell activity. METHOD OF STUDY: We tested 94 infertile women who, in spite of treatment, were unable to conceive for 6 or more months. NK-cell activity was measured by using a chromium-51 release cytotoxicity assay. with K562 human myeloid leukemia cells as targets. RESULTS: NK-cell activity of the infertile group (mean +/- SD; 40.2%+/-14.7) was significantly higher than the control group (31.5%+/-11.9, P < 0.0001). The increased NK-cell activity was not associated with age, infertile duration, depression scores, treated hyperprolactinemia, or treated endometriosis. CONCLUSIONS: In certain patients, elevated NK-cell activity may be considered an independent risk factor for infertility.

Abortion, Spontaneous↗

Sperm immobilizing antibodies in the sera of infertile women cause low fertilization rates and poor embryo quality in vitro.

PROBLEM: The effects of sperm immobilizing antibodies in the sera of infertile women on fertilization and embryo quality in vitro were investigated. METHOD OF STUDY: Before the introduction of sperm immobilization test (SIT) as a routine test for female infertility, 85 oocytes were collected in nine in vitro fertilization (IVF) cycles from four infertile women who were afterward found having had sperm immobilizing antibodies in their sera and the oocytes were inseminated with swim-up sperm in a medium containing the patient's serum. Fifty oocytes were collected in five IVF cycles from five infertile women possessing the antibodies in their sera and the oocytes were inseminated with swim-up sperm in a medium supplemented with human serum albumin (HSA). RESULTS: In the former group, 41 of 85 oocytes were fertilized, giving a fertilization rate of 48.2%. In the latter group, 43 of 50 oocytes were fertilized, giving a fertilization rate of 86.0%. There was a significant difference of the fertilization rate between the groups (P < 0.0001). Embryo quality was assessed by the Veeck's classification. The grade 1 and grade 2 embryos were considered good quality. Using this classification, 16 (39.0%) of 41 embryos incubated in the medium containing the patient's serum were good quality, while 34 (79.1%) of 43 embryos incubated in the medium supplemented with HSA were good quality. There was also a significant difference between the groups (P = 0.0003). CONCLUSIONS: These findings might indicate that sperm immobilizing antibodies in the sera of infertile women cause low fertilization rates and poor embryo quality in vitro. It is suggested that SIT in the sera of infertile women should be performed at least before proceeding IVF. The manipulation of gametes and embryos from patients having sperm immobilizing antibodies should be carefully carried out especially to avoid contaminating patient's serum and follicular fluid in the culture medium in order to have a better IVF result.

Culture Media↗

Application of DNA chip techniques for Yq microdeletion analysis in infertile males.

Our aim was to apply DNA chip technology as a diagnostic tool in infertility research and clinics. Six loci, including a sex-determining region on the Y chromosome and five sequence-tagged sites in azoospermia-factor regions were investigated in infertile male patients. Our method produced a sensitive signal, which showed the presence or absence of the STS regions on the Y chromosome. The results from 93 patients with non- obstructive azoospermia, oligoathenoteratozoospermia, or oligozoospermia were identical when analyzed with either the DNA chip technique or conventional PCR-gel electrophoresis. We have demonstrated its application in the molecular diagnosis of male infertility. This system provides an economic and high-throughput method for detecting the deletion of genomic DNA sequences of large groups of infertile patients, and a completely new approach to male infertility screening. The application of DNA chip technology to identify Yq deletions can also facilitate our understanding of male infertility.

Chromosome Deletion↗

Minimal stimulation protocol for use with intrauterine insemination in the treatment of infertility.

OBJECTIVE: To determine whether minimal stimulation with clomiphene and one injection of 150 IU of human menopausal gonadotrophin (hMG) provides pregnancy rates comparable with those in a conventional full hMG stimulation protocol for infertile patients undergoing intrauterine insemination (IUI). METHODS: A prospective study was carried out at the Infertility Clinic of a teaching institute and tertiary care referral center in Chandigarh, India. Two hundred couples with either unexplained infertility or ovulatory dysfunction cases who ovulated with clomiphene citrate (CC) but failed to conceive were offered ovarian stimulation with CC and hMG along with IUI for 420 cycles. Pregnancy rate, medication and monitoring cost were compared between minimal and conventional stimulation protocols. RESULTS: There was no difference in the couples of the two stimulation protocols regarding their age, duration and type of infertility as well as cause of infertility. Number of ampoules of hMG and monitoring costs were significantly higher in the full hMG stimulation cases whereas pregnancy rate was comparable in both protocols. CONCLUSION: Minimal stimulation appears to be an effective protocol in cases of unexplained infertility undergoing intrauterine insemination. Reduced cost and minimal monitoring is appealing to patients and the clinician.

Adult↗

Expression of IL-12, IL-10, PGE2, sIL-2R and sIL-6R in seminal plasma of fertile and infertile men.

The involvement of cytokines and other immunoregulatory factors in male infertility is still unclear. In the present study we compared the levels of IL-12, IL-10, PGE2, sIL-2R and sIL-6R in the seminal plasma (SP) of fertile and infertile men. Four groups were included: fertile donors (FERT), infertile men with azoospermia (AZOO), and infertile men with either oligoterato-asthenoazoospermia (OTA), or OTA with genital infection (OTA-INF). Cytokines and cytokine-soluble receptors in semen were evaluated by specific ELISA commercial kits. The levels of IL-12, sIL-2R and sIL-6R were similar in SP of fertile and infertile men. The mean levels of IL-10 in the SP of FERT, OTA and AZOO were 5.6 +/- 0.9, 4 +/- 2.8 and 8 +/- 3.5 pg ml-1, respectively, and did not differ significantly. The mean level of IL-10 in SP from OTA-INF (0.9 +/- 0.5 pg ml-1) was significantly lower than that for FERT (5.6 +/- 1.9 pg ml-1; P = 0.02) and AZOO (8.2 +/- 3.4 pg ml-1; P = 0.05), but not significantly different from that for OTA (3.7 +/- 2.1 pg ml-1). The mean SP level of PGE2 was significantly lower in SP of OTA-INF than FERT (7.67 +/- 2.26 and 19.67 +/- 3.69 micrograms ml-1, respectively; P < 0.02). In conclusion, the seminal plasma from fertile and infertile men contained similar levels of IL-12, sIL-2R and sIL-6R. However, the levels of IL-10 were significantly lower in SP from OTA-INF compared to FERT and AZOO. Our results indicate that specific cytokines and their soluble receptors are involved in the male reproductive system.

Dinoprostone↗

Alterations in sperm protein phosphorylation in male infertility.

Protein phosphorylation is involved in sperm capacitation, so the effect of protein phosphatase inhibitors on the capacitation of spermatozoa of males with unexplained infertility was investigated. d-mannose ligand specific receptor expression in fresh, living spermatozoa, capacitated or treated with calyculin A (an inhibitor of protein phosphatases 1 and 2A), was studied in three groups of men: pre-vasectomy (fertile) males, males in couples with male infertility, and males in couples with infertility of unknown aetiology. Flow cytometry showed significant differences between infertile couples with a male factor and fertile couples (P < 0.05), both after capacitation and after treatment with calyculin A. In the group of couples with infertility of unknown aetiology (n = 15), d-mannose receptor expression was diminished in six cases after classical capacitation. However, when the spermatozoa of these six men were treated with calyculin A, five showed an increased specific d-mannose receptor expression. From these results it is suggested that in vitro treatment of spermatozoa with inhibitors of protein phosphatases may be of great value in some cases of unexplained infertility.

Flow Cytometry↗

Apoptosis-related proteins in the testes of infertile men with varicocele.

OBJECTIVES: To assess immunohistochemically the expression of apoptosis-related proteins in the testes of infertile men, to determine which of these proteins were related to hypospermatogenesis, as a previous report suggested that apoptosis was suppressed in infertile men with varicocele. MATERIALS AND METHODS: The expression of Bcl-2, Bax, caspase-1 (ICE) and caspase-3 (CPP32) were examined in bilateral testicular specimens from 26 infertile men with varicocele and six normal testicular specimens, using the avidin-biotin-peroxidase complex method. Clinical variables were also assessed. RESULTS: Bax, ICE, and CPP32 were expressed in germ cells, while Bcl-2 was not. Differences in staining in left or right testes were not significant. In both testes of infertile patients with varicocele, significantly fewer germ cells stained for CPP32 than in controls (P < 0.001). For Bax and ICE, total germ cell staining was similar between these groups. Staining was less frequent in infertile patients for both CPP32 and ICE when the analysis was restricted to spermatogonia. Serum luteinizing hormone levels correlated positively with CPP32 staining (P = 0.0457). CONCLUSIONS: The reduced expression of CPP32 participates in regulating apoptosis in the testes of infertile men with varicocele.

Adult↗

Questionnaire survey of male infertility in cystic fibrosis.

Most male cystic fibrosis (CF) patients are infertile due to obstructive azospermia but little is known about the best time to counsel patients on infertility. All male patients attending the Adult Nottingham CF unit were invited to complete an anonymous questionnaire on infertility. The response rate was 60%. The median age that the patients first became aware of male infertility was 17 years (range 13-24) but the preferred age of receiving this information was 14 years (range 8-16). Patients first learnt about male infertility from the CF team (six patients), parents (five), from written information (two) or unexpectedly (five). Five out of 18 patients had undergone seminal analysis at a median age of 26 years but 17/18 patients felt that this should be offered routinely. Our survey has shown that patients would like infertility discussions at a younger age and routine seminal analysis.

Adolescent↗

Hyperprolactinemia and luteal insufficiency in infertile patients with mild and minimal endometriosis.

The objective of the present paper was to assess the presence of hormonal alterations in infertile women with stage I or II endometriosis (Group III, n = 20) compared to fertile women without endometriosis (Group I, n = 14) and to fertile women with endometriosis (Group II, n = 7). Serum levels of FSH, LH, estradiol, TSH, and PRL were measured between days 1 and 5 of the early follicular phase; in the luteal phase, three serum samples were collected for progesterone measurement, and endometrial biopsies were performed. Serum estradiol levels were lower (p = 0.035) in infertile patients with endometriosis than in fertile patients without endometriosis. Six infertile patients with endometriosis presented prolactin levels above 20 ng/ml. This was not observed in the other groups. Luteal insufficiency was more frequent in infertile patients with endometriosis (78.9%) than in fertile patients with (42.9%) or without endometriosis (0%). In a multiple logistic regression analysis, only the presence of endometriosis and infertility was significantly associated with luteal insufficiency. The serum levels of LH, FSH, and TSH were not significantly different among the groups. Luteal insufficiency and altered prolactin secretion were associated with endometriosis, and could be important mechanisms causing infertility in this group of patients.

Adult↗

[Laparoscopy findings in infertile women].

The results of 308 laparoscopies performed in infertile women were evaluated retrospectively. In 185 patients (60%) the laparoscopy was the last step in otherwise negative infertility evaluations (unexplained infertility). In 123 patients (40%) history or preliminary studies gave indirect evidence of possible pelvic disease. In the group of unexplained infertility laparoscopic abnormalities could be found in 50%. In 25% a tuboperitoneal factor and in 20% an endometriosis were found. Primary and secondary infertility showed the same percentage of normal findings with a higher incidence of tuboperitoneal factors in secondary infertility. In the group with indirect evidence of possible pelvic disease the incidence of positive laparoscopic findings was as high as 77%. Previous adnexitis or clinical suspicion of endometriosis (40 patients), previous pelvic operation (60 patients) and pathologic hysterosalpingographic findings (33 patients) proved to be approximately of equal prognostic value.

Adult↗

Infertility treatment is an independent risk factor for cesarean section among nulliparous women aged 40 and above.

OBJECTIVE: To determine whether nulliparous women > 40 years old with singleton pregnancies who conceived after infertility treatment are at an increased risk for cesarean section compared with older nulliparous patients who conceived spontaneously. STUDY DESIGN: All subjects in this study were nulliparous women > 40 years old with singleton gestations who were delivered of their infants between 1990 and 1998. The Mantel-Haenszel procedure was used to obtain the weighted odds ratios and to control for confounding variables. RESULTS: During the study period, 115 nulliparous women > 40 years old with singleton pregnancies were delivered of their infants in our institute. Of those, 80 pregnancies were spontaneous and 35 pregnancies occurred after infertility treatment. Women treated for infertility had a higher rate of low-birth-weight (< 2500 g) newborns (34.3% versus 10.1%; odds ratio, 4.7; 95% CI, 1.5 to 14.6; P = .002). No other statistically significant demographic and obstetric differences were found between the groups. There were no cases of perinatal death in the study population. Women treated for infertility had statistically significant higher rates of cesarean section compared with those who conceived spontaneously (71.4% versus 41.3%; odds ratio, 3.6; 95% CI, 1.4 to 9.2; P =.002). Stratified analysis (the Mantel-Haenszel technique) was used to control for possible confounders such as low birth weight, pathologic presentations, failed induction, nonprogressive labor, and nonreassuring fetal heart rate tracings. None of those variables explained the higher incidence of cesarean section in the group treated for infertility. CONCLUSION: A history of infertility treatment among nulliparous women > 40 years old with singleton pregnancies increases the risk for cesarean delivery independently of other known risk factors.

Adult↗

Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice.

Sertoli cells play a pivotal role in spermatogenesis through their interactions with germ cells. To set up a strategy for treating male infertility caused by Sertoli cell dysfunction, we developed a Sertoli cell gene transfer system by using an adenovirus vector, which maintained long-term transgene expression in the testes of infertile mice. Introduction of an adenovirus carrying the mouse Steel (Sl) gene into Sertoli cells restored partial spermatogenesis in infertile Steel/Steel(dickie) (Sl/Sl(d)) mutant mouse testes. Although these males remained infertile, round spermatids and spermatozoa from the testes produced normal fertile offspring after intracytoplasmic injection into oocytes. None of the offspring showed evidence of germ line transmission of adenoviral DNA. Thus, we demonstrate a successful treatment for infertility by using a gene therapy vector. Therefore, adenovirus-mediated gene delivery into Sertoli cells not only provides an efficient and convenient means for studying germ cell-Sertoli cell interactions through manipulation of the germ cell microenvironment in vivo, but also is a useful method to treat male infertility resulting from a Sertoli cell defect.

Adenoviridae↗

Mitochondria-related male infertility.

Approximately 15% of human couples are affected by infertility, and about half of these cases of infertility can be attributed to men, through low sperm motility (asthenozoospermia) or/and numbers (oligospermia). Because mitochondrial genome (mtDNA) mutations are identified in patients with fertility problems, there is a possibility that mitochondrial respiration defects contribute to male infertility. To address this possibility, we used a transmitochondrial mouse model (mito-mice) carrying wild-type mtDNA and mutant mtDNA with a pathogenic 4,696-bp deletion (DeltamtDNA). Here we show that mitochondrial respiration defects caused by the accumulation of DeltamtDNA induced oligospermia and asthenozoospermia in the mito-mice. Most sperm from the infertile mito-mice had abnormalities in the middle piece and nucleus. Testes of the infertile mito-mice showed meiotic arrest at the zygotene stage as well as enhanced apoptosis. Thus, our in vivo study using mito-mice directly demonstrates that normal mitochondrial respiration is required for mammalian spermatogenesis, and its defects resulting from accumulated mutant mtDNAs cause male infertility.

Animals↗

Histological analysis of endometrial curettings performed for infertility in Nigeria.

Over a 10-year period (January 1985 - December 1994) 1060 consecutive infertile patients had endometrial biopsy as part of the infertility evaluation protocol. Four hundred and six patients (38.3%) had primary infertility while 654 (61.7%) had secondary infertility. The mean age was 31.7 years. The histology results of the endometrial currettings were as follows: secretory endometrium (56.7%), endometrial hypoplasia (20%), proliferative endometrium (16.6%), pregnancy (5%) and non-specific endometritis (1.7%). Secretory endometrium was the most frequent histological finding. The employment of dilatation and curettage can inadvertently disrupt an ongoing early pregnancy, as seen from the study. In conclusion, lack of infrastructure and investigatory facilities due to poor funding makes comprehensive infertility management impossible in developing countries. In such countries, centres of excellence for infertility management should be designated together with the provision of an enabling environment for private-sector involvement.

Adult↗

Incidence of genital Chlamydia trachomatis infection in the male partners attending an infertility clinic.

Chlamydia trachomatis is an important pathogen in the aetiology of pelvic inflammatory disease, resulting in female infertility. If all female infertility patients are screened for silent genital chlamydia infection, should the male partners of these patients also be screened to decrease the risk of re-infection? To determine the incidence of current and present male infection with C. trachomatis, we carried out a prospective clinical study. We studied 100 consecutive new male partners of patients seen in the infertility clinic. The infertility was of at least 12 months duration. We used polymerase chain reaction detection of C. trachomatis in urine specimens and microimmunofluorescence serology was performed to detect both past and current infection. The female partners were also screened for chlamydia infection by cervical swabs and serology. In five male patients (5%) C. trachomatis DNA was detected in the urine specimen by polymerase chain reaction. Microimmunofluorescence serology was positive in five patients (5%). One of the subjects had positive serology and urine polymerase chain reaction testing. The proportion of male partners with current or previous C. trachomatis infection was therefore 9% (95% CI 3.39 - 14.60). Seven female patients had positive serology results (7%), one of whom also had a positive cervical swab result indicating current infection with the pathogen. In four cases, both the male and female partner had positive serology results. The cost of screening for C. trachomatis is cheaper than treating the complications of undiagnosed genital Chlamydia infection, which is implicated in tubal disease leading to infertility. The results suggest that routine screening of male partners in an infertility setting may be justified.

Adult↗

Infertility and the role of psychotherapy.

Infertility affects 6 million American women and their partners, about 10% of the reproductive age population. Recent improvements in medication, microsurgery, and assisted reproductive technology (ART) make pregnancy possible for more than half the couples pursuing treatment, yet infertility is more than a medical condition. Infertility touches all aspects of a person's life. It affects how individuals feel about themselves, their relationships, and their life perspective. Stress is only one of a myriad of emotional realities that couples facing infertility deal with, often for extended periods of time. In addition to ongoing stress, infertility creates issues of guilt, anxiety, tension within the relationship, and feelings of depression and isolation. Treating couples and individuals who are involved in the journey of dealing with infertility is an opportunity for clinical specialists in psychiatric mental health nursing. The expertise of clinical specialists both in providing psychotherapy services as well as providing a bridge of understanding of sophisticated medical and surgical procedures places them in a unique position among the various disciplines offering mental health services. This paper provides an overview of the psychological issues that play a role in psychotherapy with this population and suggests specific clinical interventions and potential role expansion for psychiatric clinical specialists.

Female↗

Alexithymia in infertile women.

OBJECTIVE: Alexithymia was compared in women with fertility disorders and fertile women who have never been confronted with fertility problems. METHOD: Self-report instruments (TAS-20 and BVAQ) were used to measure alexithymia in a group of 73 infertile women and in a comparison group of 32 fertile women. Semi-structured interviews were used to assess medical history, current and lifetime diagnosis of psychiatric disorders. RESULTS: Infertile women showed significantly higher rates of alexithymia than fertile women. The degree of alexithymia does not constitute a discriminating variable between unexplained infertile women and women with an organic aetiology of infertility. The prevalence of psychiatric diagnosis did not differ between the two groups of patients. Lifetime prevalence of depression, obsessive-compulsive disorders, post-traumatic stress disorder were statistically comparable. CONCLUSION: This result raises the question of secondary alexithymia as a coping strategy in women with fertility troubles. Given the lack of published data on alexithymia in infertile women, there is a need to replicate our results and evaluate other aspects of affect regulation in infertile patients.

Adult↗