Showing papers in "Human Reproduction in 2005"
TL;DR: A working group was convened comprised of practising gynaecologists and experts in evidence-based medicine from Europe, as well as an endometriosis self-help group representative, and the guideline was developed and refined.
Abstract: The objective was to develop recommendations for the diagnosis and treatment of endometriosis and its associated symptoms. A working group was convened comprised of practising gynaecologists and experts in evidence-based medicine from Europe, as well as an endometriosis self-help group representative. After reviewing existing evidence-based guidelines and systematic reviews, the expert panel met on three occasions for a day during which the guideline was developed and refined. Recommendations based solely on the clinical experience of the panel were avoided as much as possible. The entire ESHRE Special Interest Group for Endometriosis and Endometrium was given the opportunity to comment on the draft guideline, after which it was available for comment on the ESHRE website for 3 months. The working group then ratified the guideline by unanimous or near-unanimous voting; finally, it was approved by the ESHRE Executive Committee. The guideline will be updated regularly, and will be made available at http://www.endometriosis.org/guidelines.html with hyperlinks to the supporting evidence, and the relevant references and abstracts. For women presenting with symptoms suggestive of endometriosis, a definitive diagnosis of most forms of endometriosis requires visual inspection of the pelvis at laparoscopy as the 'gold standard' investigation. However, pain symptoms suggestive of the disease can be treated without a definitive diagnosis using a therapeutic trial of a hormonal drug to reduce menstrual flow. In women with laparoscopically confirmed disease, suppression of ovarian function for 6 months reduces endometriosis-associated pain; all hormonal drugs studied are equally effective although their side-effects and cost profiles differ. Ablation of endometriotic lesions reduces endometriosis-associated pain and the smallest effect is seen in patients with minimal disease; there is no evidence that also performing laparoscopic uterine nerve ablation (LUNA) is necessary. In minimal-mild endometriosis, suppression of ovarian function to improve fertility is not effective, but ablation of endometriotic lesions plus adhesiolysis is effective compared to diagnostic laparoscopy alone. There is insufficient evidence available to determine whether surgical excision of moderate-severe endometriosis enhances pregnancy rates. IVF is appropriate treatment especially if there are coexisting causes of infertility and/or other treatments have failed, but IVF pregnancy rates are lower in women with endometriosis than in those with tubal infertility. The management of severe/deeply infiltrating endometriosis is complex and referral to a centre with the necessary expertise is strongly recommended. Patient self-help groups can provide invaluable counselling, support and advice.
1,412 citations
TL;DR: Pooled results from all suitable published studies suggest that children born following ART are at increased risk of birth defects compared with spontaneous conceptions.
Abstract: Background The risk of birth defects in infants born following assisted reproductive technology (ART) treatment is a controversial question. Most publications examining the prevalence of birth defects in ICSI and IVF infants compared to spontaneously conceived infants have serious methodological limitations; despite this, most researchers have concluded that there is no increased risk. Methods We carried out a systematic review to identify all papers published by March 2003 with data relating to the prevalence of birth defects in infants conceived following IVF and/or ICSI compared with spontaneously conceived infants. Independent expert reviewers used criteria defined a priori to determine whether studies were suitable for inclusion in a meta-analysis. Fixed effects meta-analysis was performed for all studies and reviewer-selected studies. Results Twenty-five studies were identified for review. Two-thirds of these showed a 25% or greater increased risk of birth defects in ART infants. The results of meta-analyses of the seven reviewer-selected studies and of all 25 studies suggest a statistically significant 30-40% increased risk of birth defects associated with ART. Conclusions Pooled results from all suitable published studies suggest that children born following ART are at increased risk of birth defects compared with spontaneous conceptions. This information should be made available to couples seeking ART treatment.
652 citations
TL;DR: Under appropriate circumstances a basic infertility work-up after six unsuccessful cycles with fertility-focused intercourse will identify couples with significant infertility problems to avoid both infertility under- and over-treatment, regardless of age.
Abstract: A common definition of sub- and infertility is very important for the appropriate management of infertility. Subfertility generally describes any form of reduced fertility with prolonged time of unwanted non-conception. Infertility may be used synonymously with sterility with only sporadically occurring spontaneous pregnancies. The major factor affecting the individual spontaneous pregnancy prospect is the time of unwanted non-conception which determines the grading of subfertility. Most of the pregnancies occur in the first six cycles with intercourse in the fertile phase (80%). After that, serious subfertility must be assumed in every second couple (10%) although--after 12 unsuccessful cycles--untreated live birth rates among them will reach nearly 55% in the next 36 months. Thereafter (48 months), approximately 5% of the couples are definitive infertile with a nearly zero chance of becoming spontaneously pregnant in the future. With age, cumulative probabilities of conception decline because heterogeneity in fecundity increases due to a higher proportion of infertile couples. In truly fertile couples cumulative probabilities of conception are probably age independent. Under appropriate circumstances a basic infertility work-up after six unsuccessful cycles with fertility-focused intercourse will identify couples with significant infertility problems to avoid both infertility under- and over-treatment, regardless of age: Couples with a reasonably good prognosis (e.g. unexplained infertility) may be encouraged to wait because even with treatment they do not have a better chance of conceiving. The others may benefit from an early resort to assisted reproduction treatment.
482 citations
TL;DR: It is suggested that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR 1 could be considered a quantitative trait locus.
Abstract: BACKGROUND: Women who carry the FMR1 premutation allele have a significantly increased risk for ovarian dysfunction. We hypothesize that molecular characteristics of the FMR1 gene may explain this increased risk. METHODS: Thus, we examined the effect of FMR1 CGG repeat size and related factors on measures of ovarian dysfunction using data from 507 women with a wide range of repeat sizes. RESULTS AND CONCLUSIONS: We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR1 could be considered a quantitative trait locus. More importantly, when repeat size exceeds this threshold, the increase in risk for ovarian dysfunction is clinically significant. Intriguingly, this risk appears to plateau, or perhaps decrease, among women with very high repeats (≥ 100 repeats).
411 citations
TL;DR: The European Society of Human Reproduction and Embryology (ESHRE) as discussed by the authors developed guidelines for preimplantation genetic diagnosis (PGD), which are aimed at giving information, support and guidance to potential, fledgling and established PGD centres.
Abstract: Among the many educational materials produced by the European Society of Human Reproduction and Embryology (ESHRE) are guidelines. ESHRE guidelines may be developed for many reasons but their intent is always to promote best quality practices in reproductive medicine. In an era in which preimplantation genetic diagnosis (PGD) has become a reality, we must strive to maintain its efficacy and credibility by offering the safest and most effective treatment available. The dominant motivators for the development of current comprehensive guidelines for best PGD practice were (i) the absence of guidelines and/or regulation for PGD in many countries and (ii) the observation that no consensus exists on many of the clinical and technical aspects of PGD. As a consequence, the ESHRE PGD Consortium undertook to draw up guidelines aimed at giving information, support and guidance to potential, fledgling and established PGD centres. The success of a PGD treatment cycle is the result of great attention to detail. We have strived to provide a similar level of detail in this document and hope that it will assist staff in achieving the best clinical outcome for their patients.
393 citations
TL;DR: A significantly lower implantation rate and clinical pregnancy rate in addition to a significantly higher rate of early pregnancy loss was seen in the GnRH agonist group, most probably due to a luteal phase deficiency.
Abstract: BACKGROUND: We aimed to determine the efficacy of ovarian hyperstimulation protocols employing a GnRH antagonist to prevent a premature LH rise allowing final oocyte maturation and ovulation to be induced by a single bolus of either a GnRH agonist or hCG. METHODS: A total of 122 normogonadotrophic patients following a flexible antagonist protocol was stimulated with recombinant human FSH and prospectively randomized (sealed envelopes) to ovulation induction with a single bolus of either 0.5 mg buserelin s.c. (n = 55) or 10000IU of hCG (n = 67). A maximum of two embryos was transferred. Luteal support consisted of micronized progesterone vaginally, 90 mg a day, and estradiol, 4 mg a day per os. RESULTS: Ovulation was induced with GnRH agonist in 55 patients and hCG in 67 patients. Significantly more metaphase II (MII) oocytes were retrieved in the GnRH agonist group (P < 0.02). Significantly higher levels of LH and FSH (P < 0.001) and significantly lower levels of progesterone and estradiol (P < 0.001) were seen in the GnRH agonist group during the luteal phase. The implantation rate, 33/97 versus 3/89 (P < 0.001), clinical pregnancy rate, 36 versus 6% (P = 0.002), and rate of early pregnancy loss, 4% versus 79% (P = 0.005), were significantly in favour of hCG. CONCLUSIONS: Ovulation induction with a GnRH agonist resulted in significantly more MII oocytes. However, a significantly lower implantation rate and clinical pregnancy rate in addition to a significantly higher rate of early pregnancy loss was seen in the GnRH agonist group, most probably due to a luteal phase deficiency.
383 citations
TL;DR: Exposure to bisphenol A is associated with recurrent miscarriage and was associated with the presence of ANAs but not hypothyroidism, hyperprolactinaemia, luteal phase defects, NK cell activity or aPLs.
Abstract: Background Little is known about the influence of high exposure to bisphenol A on recurrent miscarriage and immunoendocrine abnormalities. Methods Serum bisphenol A, antiphospholipid antibodies (aPLs), antinuclear antibodies (ANAs), natural killer cell (NK) activity, prolactin, progesterone, thyroid-stimulating hormone (TSH) and free T4 were examined in 45 patients with a history of three or more (3-11) consecutive first-trimester miscarriages and 32 healthy women with no history of live birth and infertility. Subsequent pregnancy outcome and embryonic karyotype of abortuses were examined prospectively. Results The mean+/-SD values for bisphenol A in patients were 2.59+/-5.23 ng/ml, significantly higher than the 0.77+/-0.38 ng/ml found for control women (P=0.024). High exposure to bisphenol A was associated with the presence of ANAs but not hypothyroidism, hyperprolactinaemia, luteal phase defects, NK cell activity or aPLs. A high level of bisphenol A in itself did not predict subsequent miscarriage. Conclusion Exposure to bisphenol A is associated with recurrent miscarriage.
377 citations
TL;DR: Assessment of singleton ICSI and IVF 5-year-olds at 5 years of age was generally reassuring, however, it was found that ICSi children presented with more major congenital malformations and both I CSI andIVF children were more likely to need health care resources than naturally conceived children.
Abstract: BACKGROUND: Over a million children have been born from assisted conception worldwide. Newer techniques being introduced appear less and less ‘natural’, such as intracytoplasmic sperm injection (ICSI), but there is little information on these children beyond the neonatal period. METHODS: 540 ICSI conceived 5-year-old children from five European countries were comprehensively assessed, along with 538 matched naturally conceived children and 437 children conceived with standard IVF. RESULTS: Of the 540 ICSI children examined, 63 (4.2%) had experienced a major congenital malformation. Compared with naturally conceived children, the odds of a major malformation were 2.77 (95% CI 1.41– 5.46) for ICSI children and 1.80 (95% CI 0.85– 3.81) for IVF children; these estimates were little affected by adjustment for socio-demographic factors. The higher rate observed in the ICSI group was due partially to an excess of malformations in the (boys’) urogenital system. In addition, ICSI and IVF children were more likely than naturally conceived children to have had a significant childhood illness, to have had a surgical operation, to require medical therapy and to be admitted to hospital. A detailed physical examination revealed no further substantial differences between the groups, however. CONCLUSIONS: Singleton ICSI and IVF 5-year-olds are more likely to need health care resources than naturally conceived children. Assessment of singleton ICSI and IVF children at 5 years of age was generally reassuring, however, we found that ICSI children presented with more major congenital malformations and both ICSI and IVF children were more likely to need health care resources than naturally conceived children. Ongoing monitoring of these children is therefore required.
336 citations
TL;DR: Data show that ICSI with testicular spermatozoa provides the first efficient assisted reproduction treatment option for men with high levels of sperm DNA damage.
Abstract: Background Sperm DNA damage (fragmentation) is a recently discovered cause of male infertility for which no efficient treatment has yet been found. Previous findings have suggested that clinically relevant sperm DNA damage may occur at the post-testicular level. This study was undertaken to assess the clinical usefulness of ICSI with testicular spermatozoa in this indication. Methods The percentage of spermatozoa with fragmented DNA, assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling assay, and ICSI outcomes were compared in two sequential attempts performed, respectively, with ejaculated and testicular spermatozoa in 18 men with increased sperm DNA fragmentation. Results The incidence of DNA fragmentation was markedly lower in testicular spermatozoa as compared with ejaculated spermatozoa. No differences in fertilization and cleavage rates and in embryo morphological grade were found between the ICSI attempts performed with ejaculated and with testicular spermatozoa. However, eight ongoing clinical pregnancies (four singleton and four twin) were achieved by ICSI with testicular spermatozoa (44.4% pregnancy rate; 20.7% implantation rate), whereas ICSI with ejaculated spermatozoa led to only one pregnancy which was spontaneously aborted. Conclusions These data show that ICSI with testicular spermatozoa provides the first efficient assisted reproduction treatment option for men with high levels of sperm DNA damage.
323 citations
TL;DR: Most women adjusted well to unsuccessful treatment, but at follow-up, a considerable proportion still showed substantial emotional problems, which allows early identification of women at risk as well as tailored interventions.
Abstract: BACKGROUND: A longitudinal study into the course of the emotional response to IVF from pre-treatment to 6 months post-treatment and factors that contributed to that course. METHODS: A total of 148 IVF patients and 71 partners completed self-report questionnaires on anxiety, depression, personality characteristics, meaning of fertility problems, coping, marital relationship and social support at pre-treatment. Assessments of anxiety and depression were repeated immediately following the final treatment cycle and again 6 months later (follow-up). RESULTS: Women showed an increase of both anxiety and depression after unsuccessful treatment and a decrease after successful treatment. Men showed no change in anxiety and depression either after successful or after unsuccessful treatment. In the 6 months after unsuccessful treatment, women showed no recovery. At follow-up, >20% of the women showed subclinical forms of anxiety and/or depression. Personality characteristics, meaning of the fertility problems, and social support determined the course of the emotional response. CONCLUSIONS: Most women adjusted well to unsuccessful treatment, but at follow-up, a considerable proportion still showed substantial emotional problems. Personality characteristics, pre-treatment meaning of the fertility problems and social support have demonstrated the adjustment to unsuccessful IVF in women. This allows early identification of women at risk as well as tailored interventions.
320 citations
TL;DR: Both the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments.
Abstract: endometriosis-related pain over a period of six months. METHODS: Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized using a computer-generated system of sealed envelopes into either LNG-IUS (n 5 39) or GnRH analogue (n 5 43) treatment groups at three university centres. Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale (VAS), daily bleeding score was calculated from bleeding calendars, and improvement in quality of life was evaluated using the Psychological General Well-Being Index Questionnaire (PGWBI). The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis. A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period. RESULTS: CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups ( P> 0.999). In both treatment groups, women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease ( P< 0.002). LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34% and 71% of patients in the LNG-IUS and GnRH-analogue groups, respectively, reporting no bleeding during the first treatment month, and 70% and 98% reporting no bleeding during the sixth month. No difference was observed between groups with reference to improvement in quality of life. CONCLUSIONS: Both, the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments. Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years. This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive.
TL;DR: The improved cycle-to-cycle consistency of AMH as compared with other markers of ovarian follicular status is in keeping with its peculiar production by follicles at several developmental stages and further supports its role as a cost-effective, reliable marker of ovarian fertility potential.
Abstract: BACKGROUND: Our aim was to compare the intercycle reproducibility of serum anti-Mullerian hormone (AMH) measurements with that of other markers of ovarian follicular status. METHODS: Forty-seven normo- ovulatory, infertile women underwent serum AMH, inhibin B, estradiol and FSH measurements and early antral follicle (2- 12 mm in diameter) counts by transvaginal ultrasound on cycle day 3 during three consecutive mens- trual cycles. Reproducibility of measurements was estimated using intra-class correlation coefficient (ICC) calcu- lation. We also assessed the number of replicate measurements theoretically needed to reach satisfactory reliability of results. RESULTS: Serum AMH showed significantly higher reproducibility (ICC, 0.89; 95% confidence inter- val, 0.83-0.94) than inhibin B (0.76; 0.66- 0.86; P< 0.03), estradiol (0.22; 0.03- 0.41; P< 0.0001) and FSH levels (0.55; 0.39- 0.71; P< 0.01), and early antral follicle counts (0.73; 0.62-0.84; P< 0.001), and reached satisfactory reliability with a single measurement. CONCLUSIONS: The improved cycle-to-cycle consistency of AMH as compared with other markers of ovarian follicular status is in keeping with its peculiar production by follicles at several developmental stages and further supports its role as a cost-effective, reliable marker of ovarian fertility potential.
TL;DR: One in 10 IVF singletons originates from a twin gestation in early pregnancy, and spontaneous reductions that occur at >8 weeks gestation are one of the causes for the higher risk of adverse obstetric outcome in IVF singingletons.
Abstract: BACKGROUND: Spontaneous reductions are a possible cause of the increased morbidity in IVF singletons. The aim of this study was to assess incidence ra tes of spontaneous reductions in IVF/ICSI twin pregnancies and to compare short- and long-term morbidity in survivors of a vanishing co-twin with sing letons and born twins. METHODS: We identified 642 survivors of a vanishing co-twin, 5237 singleto ns from single gestations and 3678 twins from twin gestations. All children originated from pregnancies detected by transvaginal sonography in gestational week 8. By crosslinkage with the national registries the main endpoints were prematurity, birth weight, neurological sequelae and mortality. RESULTS: Of all IVF singletons born, 10.4% originated from a twin gestation in early pregnancy. Multiple logistic regression analyses adjusted for maternal age, parity and ICSI treatment showed for birth weight 8 weeks gestation. We found no excess risk of neurological sequ elae in survivors of a vanishing co-twin versus the singleton cohort; however, OR of cerebral palsy was 1.9 (95% CI 0.7–5.2). Furthermore, we observed a correlation between onset of spontaneous reduction, i.e. the later in pregnancy the higher the risk of neurological sequelae ( r = –0.09; P = 0.02). Adjusted OR of child death within the follow-up period was 3.6 (95% CI 1.7–7.6) in the survivor versus the singleton cohort. CONCLUSIONS: One in 10 IVF singletons originates from a twin gestation. Spontaneous reductions that occur at >8 weeks gestation are one of the causes for the higher risk of adverse obstetric outcome in IVF singletons.
TL;DR: Implantation and pregnancy by ICSI is associated with morphological nuclear normalcy of sperm, and the increased pregnancy outcome was attributable to the preferred nuclear morphology of the selected spermatozoa, and not to the special sperm preparation technique modified by IMSI.
Abstract: BACKGROUND: Our preceding studies have already demonstrated the advantage of intracytoplasmic morphologically selected sperm injection (IMSI) over the conventional IVF-ICSI procedure in terms of pregnancy rate. This study was undertaken to determine whether the increased pregnancy outcome was attributable to the preferred nuclear morphology of the selected spermatozoa, and not to the special sperm preparation technique modified by IMSI. METHODS: Comparison between two matched IMSI groups, i.e. negative comprising 38 cycles, where no spermatozoa with intact nuclei were available for microinjection; and positive, involving ovum microinjection by spermatozoa with strictly defined morphologically normal nuclei. RESULTS: Implantation and pregnancy rates were significantly higher, and abortion rates significantly lower, in the positive group compared with the negative group (25.0 6 25.9 versus 5.9 6 12.9%, F 5 15.8, P # 0.01; 52.6 versus 18.4%, x 2 5 9.7, P # 0.01; and 10.0 versus 57.1%, x 2 5 7.1, P # 0.02, respectively). CONCLUSIONS: Implantation and pregnancy by ICSI is
TL;DR: Three possible contenders for the replacement of CC as first-line treatment are scrutinized: metformin, aromatase inhibitors and low-dose FSH, but none of them has been proven, as yet, to be a feasible replacement for CC in this role.
Abstract: The purpose of this review is to examine whether the time has come to replace clomiphene citrate (CC) as the first line therapy for WHO group II (eu-oestrogenic) infertility, the majority of which is associated with polycystic ovary syndrome. CC has been the first line therapy for these cases for the last 40 years. It is a simple, cheap treatment, almost devoid of side effects which yields a single live birth rate of approximately 25% of starters. Non-response to CC and the gap between ovulation and pregnancy rates have variously been attributed to its anti-estrogen effects, and high LH and androgen concentrations. Three possible contenders for the replacement of CC as first-line treatment are scrutinized: metformin, aromatase inhibitors and low-dose FSH. Each has their advantages and disadvantages, but none of them, while showing much potential promise, has been proven, as yet, to be a feasible replacement for CC in this role. For CC, it may not yet be the end of an era but it may be the beginning of the end.
TL;DR: Data suggest that hysteroscopic polypectomy before IUI is an effective measure, and women in the study group had a better possibility of becoming pregnant after polypectom, with a relative risk of 2.1 (95% confidence interval 1.5-2.9).
Abstract: Background It was our intention to determine whether hysteroscopic polypectomy before intrauterine insemination (IUI) achieved better pregnancy outcomes than no intervention. Methods A total of 215 infertile women from the infertility unit of a university tertiary hospital with ultrasonographically diagnosed endometrial polyps (EP) undergoing IUI were randomly allocated to one of two pretreatment groups using an opaque envelope technique with assignment determined by a random number table. Hysteroscopic polypectomy was performed in the study group. Diagnostic hysteroscopy and polyp biopsy was performed in the control group. Results Total pregnancy rates and time for success in both groups after four IUI cycles were compared by means of contingency tables and life-table analysis. A total of 93 pregnancies occurred, 64 in the study group and 29 in the control group. Women in the study group had a better possibility of becoming pregnant after polypectomy, with a relative risk of 2.1 (95% confidence interval 1.5-2.9). Pregnancies in the study group were obtained before the first IUI in 65% of cases. Conclusions These data suggest that hysteroscopic polypectomy before IUI is an effective measure.
TL;DR: This study demonstrates that sperm DNA fragmentation, as measured by TUNEL assay, is a highly valuable indicator of male fertility.
Abstract: BACKGROUND The extent of sperm DNA fragmentation, which can be measured by the TUNEL assay, is one of the determinants of male fertility. However, the clinical application of this test to in-vivo situations is difficult owing to the absence of a statistically validated threshold value. METHODS The aim of this study was to compare the results of TUNEL assay applied to semen samples from men of proven fertility (n = 47) and patients from an infertile population (n = 66), in order to establish a discriminating threshold value. RESULTS Infertile patients had a higher mean level of DNA fragmentation than men of proven fertility (40.9 +/- 14.3% versus 13.1 +/- 7.3%, respectively; P < 0.001). The area under the receiver operating characteristics curve was 0.93 for 20% sperm DNA fragmentation. The calculated threshold value for TUNEL assay to distinguish between fertile controls and infertile men was 20%. At this threshold, specificity was 89.4 [95% confidence interval (CI) 83.7-95.1] and sensitivity was 96.9% (95% CI 93.8-100). The positive and negative predictive values of the 20% sperm DNA fragmentation threshold were high: 92.8% (95% CI 87.9-97.5) and 95.5% (95% CI 91.6-99.3), respectively. CONCLUSION This study demonstrates that sperm DNA fragmentation, as measured by TUNEL assay, is a highly valuable indicator of male fertility.
TL;DR: 90.9% of ectopic pregnancies in this study population can be accurately diagnosed using transvaginal ultrasonography prior to surgery, and the diagnosis of an ectopic pregnancy should be based on the positive visualization of an adnexal mass using TVS, to result in a decrease in the number of false positive laparoscopies.
Abstract: BACKGROUND: To evaluate the accuracy of transvaginal ultrasonography (TVS) for the detection of ectopic pregnancies (EPs) in women undergoing surgery for presumed ectopic pregnancy. METHODS: A prospective, observational study. Women were diagnosed with an EP using TVS if any of the following were noted in the adnexal region: (i) an inhomogeneous mass or blob sign adjacent to the ovary and moving separately from the ovary; or (ii) a mass with a hyper-echoic ring around the gestational sac or bagel sign; or (iii) a gestational sac with a fetal pole with or without cardiac activity. The final diagnosis was based on the findings at surgery and subsequent histology of removed tissues. RESULTS: 6621 consecutive women underwent TVS during the study; 200/6621 (3.0%) women were diagnosed as having an EP using TVS. Forty-eight non-surgically managed women were excluded from the analysis. 85.5% of women presented with symptoms and 14.5% were asymptomatic. In 88 (57.9%) cases an inhomogeneous mass or blob sign was visualized and in 20 cases (13.2%) an embryo 6 cardiac activity. Thirty-one (20.4%) had a hyper-echoic ring in the adnexa. In 11 (7.2%) cases there was no evidence of either an intra-uterine (IUP) or EP on ultrasound. Two (1.3%) IUPs were subsequently diagnosed as heterotopic pregnancies. There was no association between the presenting complaints and TVS findings. 152 surgical procedures were performed. In 5.9% (9/152) of these cases no EPs were confirmed in fallopian tube or pelvis at laparoscopy. In 9.1% (13/143) of cases an EP was visualized at surgery when not seen on the index ultrasound scan. The sensitivity and specificity of TVS to detect EP were 90.9% and 99.9%, respectively, with positive and negative predictive values of 93.5% and 99.8%, respectively. CONCLUSIONS: 90.9% of ectopic pregnancies in this study population can be accurately diagnosed using TVS prior to surgery. The diagnosis of an ectopic pregnancy should be based on the positive visualization of an adnexal mass using TVS. This should in turn result in a decrease in the number of false positive laparoscopies.
TL;DR: In this paper, a lower probability of ongoing pregnancy was expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists.
Abstract: Background Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed. Methods 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established. Results No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52). Conclusions Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists.
TL;DR: In a convenience sample of healthy non-smoking men from a non-clinical setting, higher antioxidant intake was associated with higher sperm numbers and motility.
Abstract: BACKGROUND: We seek to determine whether dietary and supplement intake of specific micronutrients (zinc and folate) and antioxidants (vitamins C, E and b-carotene) is associated with semen quality. METHODS: Ninetyseven healthy, non-smoking men provided semen and were interviewed. Average daily nutrient intake from food and supplements was derived from a self-administered food frequency questionnaire. Intake levels were summarized as low, moderate and high. Semen volume, sperm concentration, total sperm count, motility, progressive motility and total progressively motile sperm count (TPMS) were measured. RESULTS: After controlling for covariates, a high intake of antioxidants was associated with better semen quality but, in almost all cases, there was no clear dose relationship in that moderate intake groups had the poorest semen quality. For example, positive associations were observed between vitamin C intake and sperm number as reflected in the higher mean count (P 5 0.04), concentration (P 5 0.05) and TPMS (P 5 0.09); between vitamin E intake and progressive motility (P 5 0.04) and TPMS (P 5 0.05); and between b-carotene intake and sperm concentration (P 5 0.06) and progressive motility (P 5 0.06). Folate and zinc intake were not associated with improved semen quality. CONCLUSIONS: In a convenience sample of healthy non-smoking men from a non-clinical setting, higher antioxidant intake was associated with higher sperm numbers and motility.
TL;DR: Exposure to intermittent air pollution may result in sperm DNA damage and thereby increase the rates of male-mediated infertility, miscarriage, and other adverse reproductive outcomes.
Abstract: BACKGROUND: This study examined potential associations between exposure to episodes of air pollution and alterations in semen quality. The air pollution, resulting from combustion of coal for industry and home heating in the Teplice district of the Czech Republic, was much higher during the winter than at other times of year with peaks exceeding US air quality standards. METHODS: Young men from Teplice were sampled up to seven times over 2 years allowing evaluation of semen quality after periods of exposure to both low and high air pollution. Routine semen analysis (sperm concentration, motility and morphology) and tests for sperm aneuploidy and chromatin integrity were performed, comparing measurements within each subject. Exposure was classified as high or low based on data from ambient air pollution monitoring. RESULTS: Using repeated measures analysis, a significant association was found between exposure to periods of high air pollution (at or above the upper limit of US air quality standards) and the percentage of sperm with DNA fragmentation according to sperm chromatin structure assay (SCSA). Other semen measures were not associated with air pollution. CONCLUSION: Exposure to intermittent air pollution may result in sperm DNA damage and thereby increase the rates of male-mediated infertility, miscarriage, and other adverse reproductive outcomes.
TL;DR: Serum AMH levels decreased with age both in healthy women and in women with PCOS, although they were always 2- to 3-fold higher and remained elevated until 40 years of age in PCOS subjects, and the measurement of AMH could be used as a tool to assess ovarian ageing.
Abstract: BACKGROUND: Anti-Mullerian hormone (AMH) is secreted by granulosa cells of ovarian early developing fol- licles and its serum levels have been shown to correlate with small antral follicle number. Since the pronounced androgen secretion from follicles/stroma in women with polycystic ovary syndrome (PCOS) remains until late reproductive age, and since AMH reflects the number of antral follicles, it was of interest to study the possible age- related relationship between AMH, androgens and follicle number in women with PCOS and in control women. Moreover, the possible effect of metformin on serum AMH levels and the relationship to follicle count and volume were studied. METHODS: Forty-four healthy women (aged 21- 44 years) and 65 women with previously diagnosed PCOS (aged 16 -44 years) participated in the study. Serum basal AMH levels were correlated with those of serum androstenedione, testosterone, estradiol (E2), LH, FSH and inhibin B, and with follicle number. The effect of met- formin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20 - 41 years) with PCOS after 6 months of treatment. RESULTS: Serum AMH levels were 2- to 3- fold higher in PCOS women than in healthy women. In control women, serum AMH levels correlated positively with those of serum androstenedione (r 5 0.564, P< 0.001) and testosterone (r 5 0.328, P 5 0.036) and negatively with serum FSH con- centrations (r 52 0.374, P 5 0.012) and age (r 52 0.691, P< 0.001). In women with PCOS, serum AMH levels correlated positively with those of androstenedione (r 5 0.311, P 5 0.011) and testosterone (r 5 0.310, P 5 0.011) and with follicle count (r 5 0.352, P 5 0.012), and negatively with age (r 52 0.300, P 5 0.014). Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment. CONCLUSIONS: Serum AMH levels decreased with age both in healthy women and in women with PCOS, although they were always 2- to 3-fold higher and remained elevated until 40 years of age in PCOS subjects. Thus, since serum AMH levels correlate well with antral follicle count and serum androgen levels, the measurement of AMH could be used as a tool to assess ovarian ageing, to diagnose polycystic ovaries/PCOS and to evaluate treat- ment efficacy.
TL;DR: The devastating impact of smoking on the live birth rate in IVF treatment is comparable with an increase in female age of >10 years from age 20 to 30 years, and subfertile couples may improve the outcome of IVf treatment by lifestyle changes.
Abstract: Background: We investigated the separate and combined effects of smoking and body mass index (BMI) on the success rate of IVF for couples with different causes of subfertility. Methods: The success rate of IVF was examined in 8457 women. Detailed information on reproduction and lifestyle factors was combined with medical record data on IVF treatment. All IVF clinics in The Netherlands participated in this study. The main outcome measures were live birth rate per first cycle of IVF differentiated for the major predictive factors. Results: For male subfertility the delivery rate per cycle was significantly lower than unexplained subfertility, OR of 0.70 (95% CI 0.57-0.86); for tubal pathology, the delivery rate was slightly lower, OR = 0.86 (95% CI 0.70-1.01). Smoking was associated with a significantly lower delivery rate was slightly lower; for OR = 0.72 (95% CI 0.61-0.84) and a significantly higher abortion rate compared to non-smoking delivery rates of 21.4% and 16.4%, respectively (P = 0.02). Women with a BMI of ≥27kg/m2 had a significantly lower delivery rate, with an OR of 0.67 (95% CI 0.48-0.94), compared with normal weight women (BMI ≥ 20 and 10 years from age 20 to 30 years. Subfertile couples may improve the outcome of IVF treatment by lifestyle changes.
TL;DR: Poor semen quality was found to be associated with sedentary work and obesity but not with plasma levels of persistent organochlorines, and there was a significant negative correlation between semen quality parameters and body mass index.
Abstract: Background Studies have suggested that the quality of human semen has been declining over recent decades, presumably because of lifestyle or environmental factors. Methods Polychlorinated biphenyls and organochlorine pesticides were analysed in the plasma of 25 men with poor semen quality, 20 men with normal semen quality and idiopathic subfertility and 27 men with normal semen quality and female factor subfertility. Samples of seminal fluid were also analysed to assess the relationship between the levels in blood and semen. Results The results indicate no difference in the levels of organochlorines between the groups. The levels of organochlorines in seminal fluid were proportional to the levels in plasma, but approximately 40 times lower. Men with poor semen quality were three times more likely to be obese than men with normal semen quality. There was also a significant negative correlation between semen quality parameters and body mass index among men with normal semen quality. The prevalence of sedentary work was lowest among men with the best semen quality. Conclusions Poor semen quality was found to be associated with sedentary work and obesity but not with plasma levels of persistent organochlorines. More research is needed to assess whether sedentary lifestyle and obesity are causal factors in the decline of semen quality.
TL;DR: Danish register data do not support reports of an increased risk of imprinting diseases after IVF, and the incidence rate of childhood cancers, mental diseases, congenital syndromes and developmental disturbances was equal in the two groups.
Abstract: the IVF group was 0. We found a significantly increased risk of cerebral palsy in the IVF group, with a rate ratio (RR) (IVF:non-IVF) of 1.8 [95% confidence interval (CI) 1.2–2.8; P< 0.01], and of sleeping disturbances, with an RR 2.0 (95% CI 1.2– 3.3). The incidence rate of childhood cancers, mental diseases, congenital syndromes and developmental disturbances was equal in the two groups. CONCLUSIONS: We found no indication of an increased risk of imprinting diseases after IVF, but an 80% increased risk of cerebral palsy. We observed equal frequencies of childhood cancers, mental diseases, congenital syndromes and developmental disturbances in the two groups. Danish register data do not support reports of an increased risk of imprinting diseases after IVF.
TL;DR: Using a strict bioinformatics approach of microarray data, significant changes in candidate genes during the transition of the early to the mid-luteal phase of the human endometrium that may have functional significance for the opening and maintenance of the window of implantation are demonstrated.
Abstract: Background In this prospective randomized blinded clinical trial, we examined gene expression profiles of the human endometrium during the early and mid-luteal phases of the natural cycle. Methods An endometrial biopsy was performed on day 16 (LH +3) or on day 21 (LH +8), followed by RNA extraction and microarray analysis using an Affymetrix HG-U95A microchip. Data analysis was carried out using pairwise multiple group comparison with the significance analysis of microarrays (SAM) software. Results With a false discovery rate of 0, the analysis revealed that 107 genes were significantly and differently expressed (> or =2-fold) during the early versus the mid-luteal phase of the cycle. Forty-five of these genes have not been previously linked to endometrial receptivity. Validation of the microarray data was accomplished using semiquantitative RT-PCR. We demonstrated the presence of estrogen and progesterone response elements (ERE and PRE) by analysis of the 5'-flanking regions of a subset of differentially regulated genes. Conclusions Using a strict bioinformatics approach of microarray data, we demonstrated significant changes in candidate genes during the transition of the early to the mid-luteal phase of the human endometrium that may have functional significance for the opening and maintenance of the window of implantation.
TL;DR: The results suggest that low mtDNA content is associated with the impaired oocyte quality observed in ovarian insufficiency.
Abstract: BACKGROUND Mitochondrial biogenesis and bioenergetics play an important role in oocyte maturation and embryo development. We have investigated the relationship between defective mitochondrial biogenesis and the lack of oocyte maturity observed during IVF procedures with patients suffering from ovarian dystrophy and ovarian insufficiency. METHODS We used real-time quantitative PCR to quantify mitochondrial DNA (mtDNA) in 116 oocytes obtained from 47 women undergoing the ICSI procedure. We compared the mtDNA content of oocytes from women with a normal ovarian profile with that of oocytes from women with ovarian dystrophy and ovarian insufficiency. RESULTS We found an average of 256,000 +/- 213,000 mitochondrial genomes per cell. The mean mtDNA copy number was not significantly different in ovarian dystrophy compared with controls, but it was significantly lower in oocytes from women with ovarian insufficiency (100,000 +/- 99,000, P < 0.0001). CONCLUSIONS Our results suggest that low mtDNA content is associated with the impaired oocyte quality observed in ovarian insufficiency.
TL;DR: TLR4 may play an important role in modulation of immunological tolerance in the lower parts of the female reproductive tract, and in host defence against ascending infection.
Abstract: BACKGROUND: Rapid innate immune defences against infection involve the recognition of invading pathogens by specific pattern recognition receptors recently attributed to the family of Toll-like receptors (TLR). Little is known about the in vivo protein expression or distribution of TLR in the female reproductive tract in humans. It is likely that TLR distribution in the female reproductive tract reflects the immunological tolerance to the commensal organisms in lower parts of the tract (vagina, ectocervix and, partially, endocervix) and the intolerance to commensal microbial flora in the upper tract (the uterus and uterine tubes). METHODS: Using immunohistochemistry techniques, distribution of TLR1 ‐6 was studied in surgical sections from the vagina, ecto- and endocervix, endometrium and uterine tubes, obtained from patients undergoing abdominal hysterectomy for benign gynaecological conditions. RESULTS: TLR1, 2, 3, 5 and 6 were present in the epithelia of different regions of female reproductive tract. However, TLR4 was only present in the endocervix, endometrium and uterine tubes and absent in vagina and ectocervix. In addition, a secretory form of TLR4 seems to be produced by the endocervical glands. CONCLUSION: TLR4 may play an important role in modulation of immunological tolerance in the lower parts of the female reproductive tract, and in host defence against ascending infection.
TL;DR: In young women (<38 years), AFC or basal AMH and stimulated inhibin B predict ovarian response for IVF, and the only predictor for pregnancy is follicular or luteal phase AMH.
Abstract: BACKGROUND: We evaluated basal and dynamic hormonal markers [(FSH, inhibin B, estradiol and anti-Mullerian hormone (AMH)] during the follicular phase and luteal phase of the menstrual cycle and ultrasonic ovarian morphology as predictors of IVF outcome. METHODS: Fifty-six women, aged 20 oocytes) had significantly higher AFC, AMH and luteal stimulated inhibin B and estradiol than normal responders. Multivariate regression analyses showed that the best models for predicting oocyte number included AFC, follicular phase AMH and stimulated inhibin B. Only AMH showed a significant difference between pregnant and non-pregnant women at both cycle phases. CONCLUSIONS: In young women (<38 years), AFC or basal AMH and stimulated inhibin B predict ovarian response for IVF. The only predictor for pregnancy is follicular or luteal phase AMH.
TL;DR: European results of assisted reproductive techniques from treatments initiated during 2001 are presented in this fifth report, and compared with the year 2000, fewer embryos were transferred, but huge differences existed between countries.
Abstract: European results of assisted reproductive techniques from treatments initiated during 2001 are presented in this fifth report. Data were collected mainly from already existing national registers. From 23 countries, 579 clinics reported 289 690 cycles with: IVF 120 946, ICSI 114 378, frozen embryo transfer (FER) 47 195 and egg donation (ED) 7171. Overall this represents a 4% increase since the year 2000. For the first time, results on European data on intra-uterine inseminations (IUIs) were reported from 15 countries. A total of 67 124 cycles [IUI husband'sperm (IUI-H) 52 949 and IUI donor sperm (IUI-D) 14 185] were included. In 12 countries where all clinics reported to the register, a total of 108 910 cycles were performed in a population of 131.4 million, corresponding to 829 cycles per million inhabitants. For IVF, the clinical pregnancy rate per aspiration and per transfer was 25.1 and 29.0%, respectively. For ICSI, the corresponding rates were 26.2 and 28.3%. These figures are similar to the results from 2000. After IUI-H, the clinical pregnancy rate was 12.8% in women or =40 years of age. After IVF and ICSI, the distribution of transfer of one, two, three and > or =4 embryos was 12.0, 51.7, 30.8 and 5.5%, respectively. Compared with the year 2000, fewer embryos were transferred, but huge differences existed between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 74.5, 24.0 and 1.5%, respectively. This gives a total multiple delivery rate of 25.5%, compared with 26.9% in the year 2000. The range of triplet deliveries after IVF and ICSI differed from 0.0 to 8.2% between countries. After IUI-H in women <40 years of age, 10.2% were twin and 1.1% were triplet gestations.