Serological testing for celiac disease in women undergoing assisted reproduction techniques

BACKGROUND: The assertion of a causal relationship between celiac disease and infertility is suggested by several lines of research. Nevertheless, robust evidence has not yet been provided. The present study evaluated, for the first time, the prevalence of celiac disease in women undergoing assisted reproduction techniques (ART). METHODS: Serum samples from 200 Italian women undergoing ART were evaluated for celiac disease by endomisium antibody (EMA) and transglutaminase antibody (t-TGA)-two highly sensitive and specific serological markers. Two hundred women not reporting reproductive problems and having delivered at least one child served as controls. In cases of positive serology, the diagnosis was confirmed by jejunal biopsy. RESULTS: Five (2.5%) women from the study group and two (1.0%) from the control group were found to have celiac disease (P = 0.44). The main indications for ART in women found to have celiac disease were tubal factor in two cases and male infertility in three cases. None of these women reported major gastrointestinal complaints. Extra intestinal signs linked to celiac disease were noted in four out of five patients. CONCLUSION: This study raises the issue of celiac disease screening in ART programmes. Given the available evidence in the literature combined with our observations from this study, the value of serological testing for celiac disease in infertile women remains uncertain. Further studies to address this issue are required.     

Investigation of the infertile couple: investigation of the infertile couple in the era of assisted reproductive technology: a time for reappraisal

At present, several of the elements in widespread use in basic infertility testing are in dispute, marked variability exists in the work-up among specialists, and practice patterns are influenced both by modern assisted reproductive technologies (ART) and the increasing age of couples seeking help for infertility. This article is intended to stimulate the debate on a possible (lack of) usefulness of conventional methods of infertility evaluation in relation to both the modern techniques of assisted reproduction and the woman's age.     

Assisted reproduction techniques for HIV serodiscordant couples: 18 months of experience

BACKGROUND: Assisted reproduction techniques can minimize the risk of infection and treat possible sterility associated with serodiscordant couples. METHODS: We assessed the efficacy of these techniques in 57 couples in which at least one partner had human immunodeficiency virus (HIV-1) infection that was currently under control (47 men and 10 women). The semen of seropositive men was prepared and tested for viruses. Assisted reproduction techniques included intrauterine insemination (IUI), IVF and especially ICSI, with ovarian stimulation that used a long agonist protocol and recombinant FSH. Embryos were transferred on day 3 after oocyte retrieval. RESULTS: For couples with seropositive men, five IUI and 49 IVF or ICSI attempts were perfomed, whilst for seropositive women these numbers were three IUI and 12 IVF or ICSI. No pregnancy occurred following the eight IUI trials. Seroconversion was not observed in any partners of seropositive men. Efficacy of treatment for these couples with ICSI was good, the clinical pregnancy rate per embryo transfer was 48.8%. The results for seropositive women were disappointing, with a clinical pregnancy rate per embryo transfer of 9.1%. Fourteen babies from 47 treated couples have so far been born and no pregnancies from IUI. CONCLUSIONS: Assisted reproduction techniques and particularly ICSI provide HIV-1-seropositive men with a safe and highly effective means of fathering children. These techniques may be less effective for seropositive women.     

Encouraging results despite complexity of multidisciplinary care of HIV-infected women using assisted reproduction techniques

BACKGROUND: Assisted reproduction technologies can treat infertility for human immunodeficiency virus (HIV) seropositive women. We assessed the efficacy of these techniques in the results and difficulties encountered while conducting our assisted reproduction programme for 49 couples in which at least the woman had HIV infection that was currently under control. METHODS: Treatments included intrauterine insemination (IUI), IVF and ICSI, with ovarian stimulation. Embryos were transferred on day 3 after oocyte retrieval. An elective single transfer was performed, except for patients aged > or = 40 years. RESULTS: The median age of the women was 36 years. Ten IUI, nine IVF, 53 ICSI and 10 frozen-thawed embryo transfers have been performed. No pregnancy occurred following the IUI trials but for the couples with IVF and ICSI attempts the clinical pregnancy rate per embryo transfer was 23.9%. Eight babies have been born leading to a 22.2% take home baby rate per treated couple. Contamination was not observed in any newborn. CONCLUSIONS: Assisted reproduction technologies and particularly ICSI can provide HIV seropositive women with a safe means of mothering children. Results are encouraging when considering the age of the patients and a preferential single embryo transfer.     

Transmission risk of hepatitis C virus in assisted reproductive techniques

Medical assistance for procreation in a couple where one or both parents has hepatitis C viral infection (HCV) raises the issue of the transmission of the infection to the baby and/or of possible contamination of both the technicians and the gametes or embryos from virus-free parents in the laboratory. It becomes essential to assess transmission risk in assisted reproductive techniques in order to define clearly the management of couples according to their viral status. To define the HCV transmissibility risk in assisted reproduction related to the presence of virus in semen from infected infertile men, HCV RNA detection was performed in sera, and semen and sperm fractions obtained after Percoll gradient centrifugation. HCV RNA was detected in 5% (2/39) of the semen samples tested: in the raw semen, in the seminal fluid and in the cell pellet but never after Percoll selection. According to these results, we suggest a strategy for HCV-infected infertile men who need assistance for procreation.     

Chromosomal factors of infertility in candidate couples for ICSI: an equal risk of constitutional aberrations in women and men

To assess the frequency of chromosomal aberrations in French candidates for intracytoplasmic sperm injection (ICSI), and to explore the existence of a female chromosomal factor in some cases of couple infertility, a collaborative retrospective clinical and cytogenetic study was performed, launched by the Association des Cytogénéticiens de Langue Franciaise (ACLF). The karyotypes of 3208 patients [2196 men (68.4%), 1012 (31.6%) women] included in ICSI programmes over a 3-year period in France were collected. A total of 183 aberrant karyotypes was diagnosed, corresponding to an abnormality frequency of 6.1% (134/2196) for men and 4.84% (49/1012) for women. The following frequencies of abnormalities were observed respectively for men and women: 1.23% (n = 27) and 0.69% (n = 7) for reciprocal translocations, 0.82% (n = 18) and 0.69% (n = 7) for Robertsonian translocations, 0.13% (n = 3) and 0.69% (n = 7) for inversions, 3.32% (n = 73) and 2.77% (n = 28) for numerical sex chromosome aberrations, and 0.59% (n = 13) and 0% for other structural aberrations. Among the male patients of this latter group, 0.40% (n = 9) had a Y chromosome abnormality. Among the male patients with numerical sex chromosome abnormalities, 2.23% (n = 49) were 47,XXY, 0.32% (n = 7) were 47,XYY, and 0.77% (n = 17) had a mosaicism for numerical sex chromosome anomalies. All the female patients with sex chromosome abnormalities (2.77%, n = 28) had mosaicism for numerical sex chromosome anomalies. Even if these cases-the significance of which was sometimes questioned-were disregarded in the analysis, 2.08% (21/1012) of abnormal karyotypes remained in women. An overall increased frequency of chromosomal aberrations was found, and this confirmed that in some cases of poor reproductive outcome there may be a contribution of maternal chromosome aberrations. Indeed, the existence of a chromosome abnormality in the female partner was associated with the group of infertile men in which there was no apparent cause of infertility.     

Genetic sonography as the preferred option of prenatal diagnosis in patients with pregnancies following intracytoplasmic sperm injection.

The option of prenatal diagnosis with nuchal translucency measurement at 10-14 weeks of gestation and second trimester targeted ultrasound including fetal echocardiography (genetic sonography) is reported in patients after intracytoplasmic sperm injection (ICSI). From January 1995 to December 1998, 153 consecutive patients, with a mean age of 32.3 years (+/-4.1) and 29. 6% >/= 35 years, who had become pregnant after ICSI, were studied. They attended our unit for first and second trimester sonography. Of these, 67.8% of primigravid and 80.9% of nulliparous women were included. Multiple pregnancy rate was 19.7%; 189 fetuses were screened in total. Due to the introduction of genetic sonography in 1995, the rate of invasive prenatal diagnosis decreased from 74% in 1995, to 48, 36 and 19% in 1996, 1997, and 1998 respectively. Two inherited numerical and structural chromosomal anomalies in clinically healthy children at birth (1.0%) and four major malformations in all liveborn children and late abortions (2.1%) were recorded. The results demonstrate that especially in women of advanced reproductive age with a long history of infertility, detailed genetic sonography may be a reasonable and highly accepted alternative to avoid even the relatively low risks associated with invasive screening procedures.     

A critical appraisal of assisted reproduction techniques

Several treatments for infertility have been promoted with onlylittle supporting objective data demonstrating their therapeuticvalue. The choice of an assisted reproductive technique dependson a balance between numerous factors. Seldom is the choiceabsolute as in patients with tubal block. There is conflictingevidence on the efficacy of simpler methods such as ovarianstimulation with or without artificial insemination and theavailable data suggest that the more invasive methods such asgamete intra-Fallopian transfer or in-vitro fertilization aremore effective in the treatment of couples with unexplainedinfertility. Equally, there is no conclusive evidence that pregnancyrates with any of the invasive techniques are superior to anyothers. However, a higher implantation rate following tubalembryo transfers is observed in many studies. This review presentsa critical asséssment of the effectiveness of assistedreproductive techniques.     

Stronger reduction of assisted reproduction technique treatment cycle numbers in economically weak geographical regions following the German healthcare modernization law in 2004

BACKGROUND: As part of the German healthcare modernization law implemented in 2004, infertile couples face a 50% co-payment of the total assisted reproduction technique (ART) treatment costs. This has led to a drastic reduction in ART treatment cycle numbers after January 2004. The hypothesis tested in the present study was that the number of ART treatment cycles in different German federal states changed differentially after implementation of the law, depending on the economical power of the individual state in terms of gross domestic product per capita (GDP pc). METHODS: This was a retrospective data exploratory study. Data from the German IVF registry and the German Federal Statistics Office were utilized. Main outcome parameter was the proportional difference of ART treatment numbers between the time periods 2002-2003 and 2004-2005 stratified for the 16 German federal states. The federal states were grouped by Tukey-Hinges percentile analysis of GDP pc. RESULTS: The reduction of ART treatment cycle number was strongest in the lowest GDP pc group of federal states (Kruskal-Wallis P = 0.038). Mean reduction in ART cycle numbers was 51.5%, 35.7% and 38.8% in the 0-25th, 25-75th and 75-100th GDP pc percentile group, respectively. CONCLUSIONS: Conclusively, reduction in ART treatment cycle numbers following the German healthcare modernization law was significantly stronger in economically weak geographical regions.     

Relationships in couples after failed IVF treatment: a prospective follow-up study

BACKGROUND: There are few studies of couples that analyse satisfaction with treatment, adoption plans and relationships in couples after unsuccessful IVF. METHODS: ENRICH marital inventory was used to describe marital dynamics and to gain information about treatment and adoption plans. A specially designed questionnaire was used. Of the 51 couples without previous children who were asked to participate after their first failed IVF cycle, 45 participated. The next stage of the study was carried out when the couples had reached the 6 months point after the first IVF cycle, and the last stage after the couples had been through one to three treatments, 1(1/2) years after the last treatment. RESULTS: The couples displayed a stable relationship from the start as well as 1 year after the last IVF cycle. The vast majority of the couples had decided to go through with an adoption. Seventy-three per cent of the women were interested in more IVF treatment compared to 33% of the men. CONCLUSION: The stresses associated with IVF treatment did not have a negative impact on the couples' appreciation of their relationships during and after the treatment period. After treatment had been completed, the couples seemed to have reoriented themselves toward other solutions to childlessness.     

Pentoxifylline: actions and applications in assisted reproduction

Data are presented covering various studies on the use of thephosphodiesterase inhibitor pentoxifylline (PF) in the spermpreparation for procedures in assisted reproduction. Significantimprovements have been shown in the fertilization rate of oocytesalong with a reduced risk of failed fertilization cycles utilizingoligo/asthenozoospermic semen samples. Fertilization is alsoimproved for normozoospermic samples when the acrosome reactionis suboptimal. PF has proven effects on sperm motility, increasingthe proportion of hyperactivated spermatozoa. It can also enhancethe acrosome reaction and this may be the more relevant functionfor clinical prediction. There is a further action as a suppressoror scavenger of reactive oxygen species although higher concentrationsthan that in current clinical use may be required to optimizethis effect. PF should be washed out of the sample used forinsemination to avoid inhibiting the completion of oocyte maturation.     

The impact of successful assisted reproduction treatment on female and male mental health during transition to parenthood: a prospective controlled study

BACKGROUND: The dynamics of mental health during the transitionto parenthood have not been a focus of research. Our prospectivelongitudinal study was designed to reveal whether there aredifferences in mental health during the transition to parenthoodbetween parents undergoing treatment with assisted reproductiontechniques (ART) and those who conceive spontaneously. METHODS:Study group: 367 couples with a singleton ART pregnancy usingtheir own gametes. Control group: 379 couples with a spontaneoussingleton pregnancy. Men and women separately filled in questionnairesincluding the General Health Questionnaire: at the 18th–20thweek of pregnancy, 2 months postpartum and 1 year postpartum(T3). The effect of social and child-related factors on mentalhealth was examined. RESULTS: ART women had fewer depressivesymptoms during pregnancy than controls, but at T3 their depressivesymptoms were at the same level as seen in controls. Anxietysymptoms increased among control but not among ART women acrossthe transition. ART men reported generally fewer mental healthsymptoms than their controls. Social and child-related stressorshad negative impacts on mental health changes among controlcouples, whereas no impact was found among ART couples. CONCLUSIONS:Successful ART did not predict mental health problems duringthe transition to parenthood. Moreover, ART couples’ mentalhealth was remarkably resistant to social and child-relatedstress during the transition to parenthood.     

The effect of anxiety and depression scores of couples who underwent assisted reproductive techniques on the pregnancy outcomes

ObjectiveThe aim of this study was to determine the effect of anxiety and depression scores of couples who underwent Assisted Reproductive Techniques (ART) on pregnancy outcomes.MethodThis study was conducted as a prospective and comparative study with 217 couples. The study data was collected by using a semi-structured questionnaire and the Turkish version of the State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). The questionnaire, STAI and BDI were applied to couples who initiated ART treatment. Couples'' state anxiety scores were re-evaluated after embryo transfer (ET).ResultsA significant relationship was found between the depression score of women and pregnancy outcome (p < 0.05). It was determined that anxiety scores for both men and women were higher before the ART procedure, but their anxiety scores decreased after ET (p < 0.05). Spouses of women with a negative pregnancy outcome had higher trait and state anxiety mean scores (p > 0.05) and lower depression scores (p <0.05) than spouses of women with a positive pregnancy outcome.ConclusionStudy results indicated that the anxiety and depression scores of couples who had achieved a positive pregnancy result were lower than for couples with a negative result. The results of this study will contribute to the health professionals especially to the nurses who spend the most time with couples in providing consulting services and supporting psychological status of couples during ART process in Turkey.     

男性不育患者精子染色体畸变及精子DNA完整性分析

目的 探讨男性不育患者精子染色体和精子DNA完整性的改变.方法 精子染色质扩散(sperm chromatin dispersion,SCD)实验分析精子DNA碎片,正常生育男性(对照组)32名,特发性严重少弱精子症患者(idiopathic severe oligoasthenozoospermia,ISOA)19例,妻子不明原因反复自然流产(unexpbined recurrent miscarriage,URM)38例;多色荧光原位杂交(fluorescent in situ hybridization,FISH)技术检测URM妇女丈夫(n=12)、ISOA不育者(n=10)及对照组(n=5)精子13、21、18、X和Y染色体畸变.结果 对照组、ISOA不育者及URM妇女丈夫精子13、18和21染色体数目总体异常的比率分别为1.29%、4.02%和3.91%,而X和Y染色体数目总体异常的比率分别为0.61%、2.03%和1.98%,与对照组比较差异均有统计学意义(P＜0.01).SCD实验分析精子DNA碎片,ISOA不育患者(n=19)及URM妇女丈夫(n=38)精子DNA碎片比例平均为40.7%±17.8%和22.1%±10.3%,均显著性高于对照组(12.1%±5.2%,P＜0.01).FISH精子染色体(13、21、18、X和Y探针)数目畸变率与精子DNA碎片比率呈正相关(r=0.874,P＜0.01,n=27),精子DNA碎片比率与精子密度及前向运动精子率呈负相关(r=-0.571,P＜0.01,和r=-0.616,P＜0.01,n=89),与畸形精子比率呈正相关(r=0.637,P＜0.01,n=89).结论 精子染色体畸变率和精子DNA碎片比率增高,可能是ISOA和妻子URM不育男性的原因之一,精子DNA损伤筛查町能为特发性男性不育患者提供有用的信息.     

Economic implications of assisted reproductive techniques: a systematic review

BACKGROUND: Approximately one in six couples experiences problems with their fertility at some point in their reproductive lives. The economic implications of the use of assisted reproductive techniques require consideration. Herein, the health economics research in this area are critically appraised. METHODS: Multiple strategies were used to identify relevant studies. Each title and abstract was independently reviewed by two members of the study team and categorized according to perceived relevance. The selected papers were then assessed for quality and data were extracted, converted to UK pounds sterling at 1999/2000 prices, tabulated and critically appraised. RESULTS: A total of 2547 papers was identified through the searches; this resulted in 30 economic evaluations, 22 cost studies and five economic benefit studies that met the selection criteria. The quality of these studies was mixed; many failed to disaggregate costs, discount future costs or conduct sensitivity analyses. Consistent findings included the following: initiating treatment with intrauterine insemination appeared to be more cost-effective than IVF; vasectomy reversal appeared to be more cost-effective than ICSI; factors associated with poor prognosis decreased the cost-effectiveness of interventions. CONCLUSIONS: The cost-effectiveness of different interventions should be considered when making decisions about treatment. Future economic appraisals of assisted reproductive techniques would benefit from more robust methodology than is evident in much of the published literature to date.     

Low-level sex chromosome mosaicism in female partners of couples undergoing ICSI therapy does not significantly affect treatment outcome

BACKGROUND: There is an increased rate of chromosomal anomalies, in particular low-level sex chromosome mosaicism, in the female partners of couples undergoing intracytoplasmic sperm injection (ICSI). METHODS: Among 811 consecutive couples presenting for pre-ICSI chromosome analysis, chromosomal abnormalities were detected in 54 individuals, of which 26 were low-level sex chromosome mosaicism in the females. Attention was focused on the treatment course and outcome of ICSI in 20 couples with low-level sex chromosome mosaicism in the females actually embarking on ICSI treatment (group I, n = 38 ICSI treatment cycles). Applying a case-control design, each of the 20 couples was matched according to female age and source of spermatozoa to couples without a chromosomal abnormality in either of the partners (group II, n = 38 ICSI treatment cycles). RESULTS: No significant differences were found between the groups in ovarian response, fertilization rate and number of embryos transferred. Pregnancy rates, as well as implantation and abortion rates did not differ significantly between the groups. CONCLUSIONS: The data suggest that low-level sex chromosome mosaicism in females has no major effect on the course and outcome of ICSI.     

810例严重少(无)精子症患者Y染色体微缺失筛查与分析

目的筛查原发无精子症与重度少精子症患者Y染色体微缺失情况,探讨Y染色体微缺失与男性不育的关系。方法采用改良多重PCR方法对810例男性不育患者(457例原发无精子症和353例严重少精子症)基因组DNA进行Y染色体微缺失筛查。结果810例患者中发现77例Y染色体微缺失患者,缺失率为9.5%,其中少精子症31例,均为AZFc微缺失,无精子症46例,缺失类型呈多样化。缺失类型包括AZFa微缺失3例(3.90%),AZFb微缺失2例(2.60%),AZFc微缺失63例(81.82%),AZFb+c微缺失4例(5.19%),AZFa+b+c微缺失5例(6.49%)。结论Y染色体微缺失是原发无精子症和少精子症的重要原因之一,AZFc缺失为最常见的缺失类型,对此类患者进行Y染色体微缺失的常规筛查是有必要的,尤其是拟行辅助生殖技术助孕的不育患者。     

Possibilities and limitations of techniques of assisted reproduction for the treatment of male infertility

Since relatively few spermatozoa are needed for oocyte fertilization during gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF), these methods have been applied in couples with infertility due to male causes. Forty-six couples with male factor infertility were enrolled in this study and results were compared with those attained in 48 couples treated with the same techniques for other than male causes. Overall, GIFT resulted in 26% ongoing pregnancies. GIFT seems to be particularly successful when the sperm concentration is 20 x 10(6)/ml or more, but sperm motility and/or morphology are poor. Nine pregnancies occurred out of 26 GIFT cycles in 18 cases selected on this basis. The ongoing pregnancy rate after IVF was 16% per patient. The latter treatment should be attempted in male immune infertility and in cases with a low sperm concentration, with or without abnormal sperm motility and/or morphology. In these circumstances, five pregnancies were attained out of 28 cycles in 14 cases. For similar sperm concentrations, the conception rate per cycle attained with techniques of assisted reproduction was more than twice that attained with conventional treatment of male infertility.     

Results of assisted reproductive technique in men with cystic fibrosis

BACKGROUND: Sterility in men with cystic fibrosis (CF) raises the question of the use of assisted reproductive techniques (ART). A multidisciplinary network including adult CF centre and reproductive medicine units was set up to answer requests for ART. METHODS: This retrospective study included 25 men with CF between 1994 and 2004. Clinical status, semen analysis, CF mutations analysis and artificial insemination by donor (AID) or ICSI after surgical retrieval of sperm were monitored. RESULTS: All CF men had azoospermia. Two chose AID first (one delivery); 23 chose ICSI. Sperm were surgically retrieved in 21 cases, and ICSI was performed in 19. Pregnancies occurred in 12 of these 19 couples (63%) (two ectopic pregnancies, two spontaneous abortions, one termination of pregnancy for polymalformed twins and 11 single deliveries in nine couples). Two couples tried AID after ICSI failed; one had twins. Another adopted a child, and two had a spontaneous pregnancy. After a follow-up of 4.1+/-2.3 years, two patients died, two underwent lung transplantation and 21 remained stable. CONCLUSION: ART can help men with CF to become a father, but their health status and short survival need careful counselling and multidisciplinary medical care.     

The prognostic value of basal luteinizing hormone:follicle-stimulating hormone ratio in the treatment of patients with polycystic ovarian syndrome by assisted reproduction techniques

One of the main endocrinological disturbances in patients withpolycystic ovarian syndrome (PCOS) is the increased baselineconcentrations of luteinizing hormone (LH) and consequentlya high LHrfollicle-stimulating hormone (FSH) ratio. The aimof this study was to assess the relationship between the baselineLH:FSH ratio with the stimulation response and the miscarriagerisk in PCOS women stimulated for assisted reproduction techniques(ART) with and without gonadotrophin-releasing hormone analogue(GnRHa). Two groups of PCOS patients were analysed retrospectively.Group A (n = 20, 20 cycles) consisted of women stimulated withhuman menopausal gonadotrophin (HMG), and group B (n = 128,162 cycles) comprised women stimulated with buserelin-long/HMG.LH and FSH concentrations were measured during the early follicularphase (days 4–6) in a preceding spontaneous or progestininducedcycle. The following parameters were assessed: number of folliclesdeveloped, number of oocytes obtained and percentage of matureoocytes, as well as number of abortions and live births. Ingroup A, the baseline LH:FSH ratio was correlated inverselywith the number of follicles developed (P < 0.05), the numberof oocytes obtained (P < 0.05) and the percentage of matureoocytes (P < 0.05). In group B, no correlation was foundbetween the LH:FSH ratio and the number of follicles and oocytes,because their numbers were relatively constant irrespectiveof the baseline LH:FSH ratio, but a significant inverse correlationwas noted with the percentage of mature oocytes (P < 0.001).However, a comparison of the slopes of the curve indicated abetter correlation between the LH:FSH ratio and the percentageof mature oocytes in group A than in group B (P < 0.05).These findings were also confirmed when patients were subdividedaccording to the LH:FSH ratio (<3 or 3=3). Furthermore, inwomen who miscarried, the mean LH:FSH ratio was significantlyhigher than in women having a live birth. In conclusion, inPCOS patients stimulated with HMG, a high basal LH:FSH ratioappears to have an adverse effect on the number of folliclesand oocytes, as well as on oocyte maturity. On the other hand,the administration of GnRHa in the long protocol seems to reversethis detrimental effect on follicle and oocyte development.Furthermore, a higher LH:FSH ratio seems to predict a greaterpossibility for miscarriage, despite the use of GnRHa.