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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.

Adoption↗

Cell-free fetal DNA levels in pregnancies conceived by IVF.

BACKGROUND: Increased second-trimester levels of maternal serum HCG in IVF conceptions lead to an increased false-positive rate in Down syndrome screening. Increased levels of cell-free fetal DNA (cffDNA) in maternal plasma have been correlated with increased HCG levels. Our aim was to determine whether cffDNA levels are elevated in IVF pregnancies compared with natural pregnancies. METHODS: Sixteen archived second-trimester serum samples from IVF pregnancies were matched with five control samples from naturally conceived pregnancies per case, all carrying a singleton male fetus. cffDNA concentrations were measured by real-time PCR amplification of a Y chromosome sequence and compared with four standard second trimester serum screening markers (alpha-fetoprotein, estriol, HCG and inhibin A). RESULTS: Mean cffDNA levels for cases and controls were 57.9 and 57.1 genome equivalents/ml, respectively (P = 0.95). Mean observed rank (from 1 to 6) of cffDNA was 3.625 in the IVF conceived group, compared with an expected value of 3.5 (P = 0.53). No significant correlations were observed between cffDNA and serum markers. CONCLUSIONS: IVF does not affect levels of cffDNA, which appears to be independent of traditional screening markers (e.g. HCG). Therefore, cffDNA can be used as an additional serum marker (e.g. Down syndrome screening) without adjustment for IVF pregnancies.

Biomarkers↗

The psychological impact of mild ovarian stimulation combined with single embryo transfer compared with conventional IVF.

BACKGROUND: The objective of this study was to assess the psychological implications of mild ovarian stimulation combined with single embryo transfer (SET) during a first IVF cycle. METHODS: We conducted a randomized controlled two-centre trial. Three hundred and ninety-one couples were randomized to undergo either mild ovarian stimulation with GnRH antagonist co-treatment and SET (n=199) or conventional GnRH agonist long protocol ovarian stimulation with double embryo transfer (DET) (n=192). Women completed the Hospital Anxiety and Depression Scale, the Hopkins Symptom Checklist and the Subjective Sleep Quality Scale at baseline, on the first day of ovarian stimulation and following embryo transfer. Affect was assessed daily with the Daily Record Keeping Chart from the first day of ovarian stimulation until the day treatment outcome became known. RESULTS: The conventional IVF group experienced elevated levels of physical and depressive symptoms during pituitary downregulation. At oocyte retrieval, this group experienced more positive affect and less negative affect than the mild IVF group. In the conventional IVF group, cycle cancellation was associated with less positive and more negative affect. CONCLUSIONS: During the first IVF treatment cycle, mild ovarian stimulation and SET does not lead to more psychological complaints than conventional IVF.

Anxiety↗

The endometrium in stimulated cycles for IVF.

Ovarian stimulation for IVF is known to affect luteal phase function. The endometrium in IVF cycles is thus subject to an altered endocrinological environment and to a possible direct effect of the ovarian stimulation therapy. Factors influencing the endometrial receptivity in such cycles are poorly understood. Studies comparing the endometrium in IVF cycles with natural cycles as controls have shown premature secretory changes in the post-ovulatory and early luteal phase of IVF cycles, followed by a large proportion of dyssynchronous glandular and stromal differentiation in the mid-luteal phase. These findings suggest a profound modification of luteal endometrial development in stimulated cycles. This hypothesis is further supported by the demonstration of a modified endometrial steroid receptor regulation and a profound antiproliferative effect in IVF cycles. The time of maximal endometrial receptivity is defined as the implantation window and is characterized by the expression of various endometrial products, among which pinopodes, integrins and leukaemia inhibitory factor are best described. Premature expression of pinopodes and integrins are in line with the observation of precocious luteal transformation following ovarian stimulation, although the clinical relevance with respect to the establishment of a clinical pregnancy awaits further validation. Studies exploring the endometrium within the cycle of embryo transfer have shown a deleterious effect of severe peri-ovulatory maturation advancement exceeding 3 days, as no clinical pregnancies were obtained in this condition. Further unravelling of molecules involved in the implantation mechanism is needed for a better comprehension of the link between altered endometrial development and receptivity in IVF cycles.

Embryo Implantation↗

Female and male lifestyle habits and IVF: what is known and unknown.

There is no greater tribute to the importance and efficacy of IVF than the fact that >1 x 10(6) babies have been born to infertile couples since its clinical introduction in 1978. Despite enormous advances regarding the technical aspects of the IVF procedure, the parents' contribution has virtually been ignored when considering aspects that influence success rates. This systematic review focuses on the effects of female and male lifestyle habits (specifically: smoking, alcohol and caffeine use, and psychological stress) on the reproductive endpoints of IVF (i.e. oocyte aspiration, fertilization, embryo transfer, achievement of a pregnancy, live birth delivery, and perinatal outcomes, e.g. low birthweight, multiple gestations). What is currently known in the field of lifestyle habits and IVF? There is compelling evidence that smoking has a negative influence on IVF outcomes, whereas for stress, the evidence is suggestive but insufficient due to the heterogeneity of studies. The evidence for the effects of alcohol and caffeine on IVF is inadequate, and therefore unknown, due to the scarcity of studies.

Abortion, Spontaneous↗

Women's emotional adjustment to IVF: a systematic review of 25 years of research.

This review provides an overview of how women adjust emotionally to the various phases of IVF treatment in terms of anxiety, depression or general distress before, during and after different treatment cycles. A systematic scrutiny of the literature yielded 706 articles that paid attention to emotional aspects of IVF treatment of which 27 investigated the women's emotional adjustment with standardized measures in relation to norm or control groups. Most studies involved concurrent comparisons between women in different treatment phases and different types of control groups. The findings indicated that women starting IVF were only slightly different emotionally from the norm groups. Unsuccessful treatment raised the women's levels of negative emotions, which continued after consecutive unsuccessful cycles. In general, most women proved to adjust well to unsuccessful IVF, although a considerable group showed subclinical emotional problems. When IVF resulted in pregnancy, the negative emotions disappeared, indicating that treatment-induced stress is considerably related to threats of failure. The concurrent research reviewed, should now be underpinned by longitudinal studies to provide more information about women's long-term emotional adjustment to unsuccessful IVF and about indicators of risk factors for problematic emotional adjustment after unsuccessful treatment, to foster focused psychological support for women at risk.

Anxiety↗

Influence of sperm parameters on outcome of subzonal insemination in the case of previous IVF failure. off.

Subzonal insemination (SUZI) has been proposed for patients with sperm male factor infertility, and in cases of in-vitro fertilization (IVF) failures. However despite SUZI, there still remain couples with very low fertilization rates and even with fertilization failures. Since sperm parameters are known to influence the IVF fertilization rate, we investigated the relation between sperm parameters and the SUZI issue in cases of previous IVF failures with normal or subnormal sperm. Twenty-seven couples were included in the study and were split into two groups according to whether they had normal or subnormal sperm. In the first part of the study a randomized prospective trial comparing SUZI to classic IVF insemination was carried out (11 cycles). In the second part, all the oocytes had SUZI (35 cycles). None of the control inseminated oocytes fertilized. Including all the cases, the fertilization rate after SUZI was 29.8% with a pregnancy rate of 15.2% per cycle. We concluded that: (i) SUZI is efficient for achieving fertilization in cases of IVF failures; (ii) the post SUZI fertilization rate is inversely correlated to the percentage of acrosome defects in the semen (P < 0.001); and (iii) when the sperm is normal, the oocyte quality might be responsible for the previous IVF failures. In spite of a good fertilization rate for this indication, it seems that the chance of having a baby is low.

Adult↗

The early history of IVF in Australia and its contribution to the world (1970-1990).

Although Edwards and Steptoe achieved the first IVF pregnancy and birth in 1978, the majority of pioneering developments in IVF during the eighties came from Australia. They included the world's first donor egg pregnancy, the first frozen embryo pregnancy and the first IVF multiple pregnancies. Australia also produced the first national guidelines for IVF practices, the first statute legislation protecting donor gamete pregnancies, and Victoria proclaimed the first statute legislation regarding control of IVF procedures. The reporting of the outcome of all IVF pregnancies began in 1980 as another world initiative.

Australia↗

Clinical experience with IVIg Rx in patients with prior failed IVF pregnancies: report of 30 consecutive patients.

PROBLEM: This study reviews one practitioner's experience with intravenous immunoglobulin (IVIg) therapy in the in-vitro fertilization (IVF) cycles of 30 patients with previous IVF failures. METHOD OF STUDY: Thirty patients had undergone 82 prior assisted reproductive technology (ART) cycles (mean 3.9 +/- 2 failed ART cycles, median 3.0, range 1-8) yielding one term birth, one loss at 22.5 weeks, and five chemical pregnancies. These patients underwent comprehensive clinical and laboratory evaluation, including immunologic workup, and were accepted for IVIg therapy in their next IVF cycle. RESULTS: A total of 40 cycles were treated. Twenty-four (60%) of the IVIg-treated IVF cycles showed a positive human chorionic gonadotropin test. Comparing the IVIg cycles to the untreated ART cycles, there were no differences in the number of embryos transferred, fertilized embryos, or eggs. Eighty-six percent of the cases with confirmed implantation delivered; there was one chemical pregnancy, one 20-week spontaneous fetal death, and one trisomy. Five (24%) of the 21 pregnant patients delivered at 30-36 weeks. The remaining 13 delivered at term. Only three (11%) had no positive immune test. CONCLUSION: In what may be a selected population of IVF patients (with high incidence of abnormal immune testing), early IVIg therapy may be associated with the improved success of IVF, and the high rate of live birth.

Adult↗

Resistin levels of serum and follicular fluid in non-obese patients with polycystic ovary syndrome during IVF cycles.

OBJECTIVES: To measure serum and follicular resistin, steroids hormone levels in women with PCOS (polycystic ovary syndrome) (BMI (body mass index)<25 kg/m(2)), to assess possible correlations of resistin to hormonal and metabolic parameters and to analyze the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) in women with PCOS and tubal infertility. STUDY DESIGN: We analyzed the clinical outcomes of IVF-ET in women with PCOS (BMI<25 kg/m(2)) and tubal infertility during the years 2002 to 2004 and compared the serum and follicular fluid resistin levels, estradiol (E(2)), progesterone (P), testosterone (T) levels in 20 PCOS and 20 healthy, age-matched women without PCOS during IVF-stimulated cycles. The correlations between the resistin levels and the outcomes of IVF-ET were evaluated. RESULTS: No significant differences in resistin levels of either serum or follicular fluid between PCOS and control group were found. However, resistin levels in serum were higher than that in follicular fluid in both groups. Multiple regression analysis showed that resistin levels in serum did not correlate with BMI, estradiol, LH (luteinizing hormone) and insulin level in fasting blood. No significant correlations were found between follicular fluid reisistin levels and fertilization rate, implantation rate, clinical pregnancy rate or early miscarriage rate in both PCOS and control groups. CONCLUSION: Our results show that resistin does not have correlation with the hormonal and metabolic parameters as well as the outcomes of IVF. These data suggest that resistin is unlikely to be a local determinant factor in steroidogenesis and growth and maturation of oocytes during IVF-ET in lean women with PCOS.

Adult↗

Triplets and quadruplets born in Victoria between 1982 and 1990. The impact of IVF and GIFT on rising birthrates.

OBJECTIVES: To examine the perinatal characteristics of all higher order multiple births (133 sets of triplets and six sets of quadruplets) in the State of Victoria between 1982 and 1990. To compare the rising higher order multiple birth rates in Victoria with those in the other States of Australia, and to assess the impact of in-vitro fertilisation (IVF) and gamete intrafallopian transfer (GIFT) on these rising birth rates. DESIGN: Retrospective review of all higher order multiple births registered in Victoria and other States of Australia between 1982 and 1990, and in particular those resulting from IVF and GIFT. DATA SOURCES: Victorian Perinatal Data Collection Unit, Australian Bureau of Statistics, National Perinatal Statistics Unit, data from Victorian IVF and GIFT units. MAIN OUTCOME MEASURES: Higher order multiple birth rates and perinatal mortality rates. RESULTS: The higher order multiple birth rates in Victoria rose from 3.5 per 10,000 in 1982 to 10.9 per 10,000 in 1990. The average perinatal mortality rates for the Victorian triplets and quadruplets born during this period were 10.8% and 25.0%, respectively. The rates of caesarean section were 70% and 83%; the proportions of deliveries in level III hospitals, 75% and 100%; and the mean maternal lengths of stay in hospital, 32 and 57 days, respectively. Endotracheal intubation was performed at birth in 18.5% of all infants. The proportions of triplet and quadruplet pregnancies in Victoria owing to IVF and GIFT rose during this period, reaching a peak of 42% in 1990. In the other States, the birth rates for higher order multiples increased at 1.8 times the rate observed for Victoria, with IVF and GIFT contributing to an estimated 43% of these conceptions between 1985 and 1989. CONCLUSION: Restrictions on the numbers of embryos/oocytes transferred during IVF and GIFT should reduce the frequency of higher order multiple births.

Adult↗

The mother-child relationship following in vitro fertilisation (IVF): infant attachment, responsivity, and maternal sensitivity.

Infant attachment and mother-child interaction were evaluated for 65 primiparous women and their singleton infants conceived through in vitro fertilisation (IVF) and a control group of 61 women and their infants conceived naturally. The sample was enrolled during pregnancy as part of a longitudinal study. At 12 months postpartum, security of infant attachment was assessed using the Strange Situation procedure, and mother-child interaction was assessed in a free play context using the Emotional Availability Scales. IVF children demonstrated predominantly secure attachment relationships with their mothers (64.6% IVF, 55.9% controls), and there were no significant between-group differences in the proportion of IVF compared to control group children classified in any of the secure or insecure attachment groups. Furthermore, there were no significant group differences on maternal (sensitivity, structuring, hostility) or child (responsivity, involving) dimensions of interaction during play. The majority of IVF mothers (86%) were sensitive and their infants responsive (91%). Contrary to expectation, mother's ratings of greater anticipated infant difficultness assessed during pregnancy and higher ratings of infant temperament and behaviour difficulty assessed at 4 and 12 months postpartum were associated with secure attachment relationships and more optimal mother-child interaction in both the IVF and control groups.

Adult↗

[Effect of salpingectomy on the results of IVF in women with tubal sterility--prospective study].

OBJECTIVE: To compare the IVF results after salpingectomy of hydrosalpinges visible on ultrasound with IVF results in women with tubal infertility but without hydrosalpinx. DESIGN: Prospective study. SETTING: Sanatorium Pronatal, Na Dlouhé mezi 4/12, 147 00, Praha 4. METHODS: 101 women with tubal factor infertility were evaluated. In a prospective study we compared the results of first IVF cycle after salpingectomy of hydrosalpinges visible on ultrasound performed in 51 women (study group) with IVF results of 50 women with tubal infertility (confirmed by HSG and laparoscopy) but without hydrosalpinges and without salpingectomy. RESULTS: The maternal age in both groups (32.4 +/- 3.9 in salpingectomy group and 33.0 +/- 4.1 in control group), maximum estradiol levels (1392.6 +/- 675.8 pg/ml in salpingectomy group vers. 1624.7 +/- 909.7 pg/ml in control group), number of oocytes (11.3 +/- 5.8 after salpingectomy vers. 11.0 +/- 6.1 in controls), number of embryos generated (7.1 +/- 4.6 vers. 7.9 +/- 4.7) and number of embryos transferred were not statistically different. In their first IVF cycle after salpingectomy has been performed 30 women out of 51 became clinically pregnant (58.8%), while in control group a clinical pregnancy could be verified in 16 women (32.0%). Implantation rate in women after salpingectomy was 28.2% vers. 12.3% in control group. Both implantation rate and pregnancy rate were statistically different at 5% level of significance. CONCLUSION: After salpingectomy of hydrosalpinges visible on ultrasound the implantation rate and clinical pregnancy rate are significantly better when compared to IVF patients with tubal infertility without the presence of hydrosalpinges and without salpingectomy. Salpingectomy should be offered to all patients with hydrosalpinges visible on ultrasound. Moreover, this radical approach should be considered even in women with highly damaged tubes but without the presence of hydrosalpinges.

Adult↗

Converting an IVF cycle to IUI in low responders with at least 2 follicles.

OBJECTIVE: To assess the utility of transforming an in vitro fertilization (IVF) cycle with low ovarian response to an intrauterine insemination (IUI) cycle. STUDY DESIGN: The inclusion criteria were women undergoing IVF because of idiopathic infertility, a mild to moderate male factor or IUI failure, with at least 1 normal, patent tube. When ovarian stimulation produced 2-4 follicles > or = 18 mm, the IVF cycle was converted to an IUI cycle. In cases with 4 follicles, estradiol had to be < 800 pg/mL. A total of 57 cycles were analyzed. RESULTS: The clinical pregnancy rate (PR) was 14.0% (8/57) in IVF cycles converted to IUI vs. 17.3% in our general IUI population (240/1,389). Converted cycles were associated with longer ovarian stimulation and with lower estradiol levels and less mature follicles than was IUI in the general population. There was a trend toward higher PR in women starting ovarian stimulation with 225 IU of gonadotropins (18.2%) than in those starting with higher doses (8.6%) (P > .05). CONCLUSION: In IVF low responders with at least 1 normal, patent tube when 2-4 follicles are observed, converting the IVF cycle to an IUI cycle yields a PR of 14.0%. This option should be considered in the management of low responders, especially those not stimulated with high doses of gonadotropins.

Adult↗

[Results of IVF in women with endometriosis].

When associated with infertility, endometriosis often requires in vitro fertilization (IVF). The need of IVF instead of other Assisted Reproductive Technologies is correlated with the severity of the lesions and associated tubal pathology. Results of IVF (in terms of pregnancy rates), are influenced by the existence of endometriosis, but this influence remains controversial, and focused on three possible points: poor ovarian reserve (and ovarian response), poor quality of oocytes and embryos, poor implantation. It seems that mild and moderate endometriosis (I-II American Fertility Society score) has few deleterious effect on ovarian reserve, ovarian response, and pregnancy rates. All these parameters are decreased by the existence of severe endometriosis (III-IV AFS). Its surgical treatment appears to improve the results of IVF, notably in women under 35. But iterative surgery of endometriomas might be deleterious for ovarian function. Previous treatment by Gn-RH agonists also improves the outcome of IVF, whereas ICSI does not modify either the biological parameters, nor the pregnancy rates. Ovarian hyperstimulation in women with endometriosis might increase the severity of the lesions and the risk of complications: the use of unstimulated cycle (n-IVF) in young patients with normal ovarian reserve might be interesting.

Endometriosis↗

[IVF failures: maternal thrombophilia as a possible cause].

It is studied the association between thrombophilia and failure to achieve pregnancy after IVF. The study group included 55 patients aged 24-45 years, with history of infertility I and II (unexplained genesis). 38 women were with a history of IVF failures and 17 -- without such history. The comparison group consisted of 30 women pregnant after IVF (male factor). The control group was comprised of 50 patients with physiological course of pregnancy. In the study group thrombophilia was verified in 90% of cases; in the group of comparison -- 30%; in control group -- 26% (p<0,05). In the study group the multigenic defects were verified in 90% of cases. The polymorphism of PAI-1 was found in 69% women with a history of IVF failures and in 35% in group without the history of IVF failures. In the group of comparison polymorphism was found in 10% of women and in control group -- 8% (p<0,05). In the study group differential antibiotic prophylaxis was conducted with the result of 36,4% viable pregnancy (20 women of 55). The endpoint for success was a live birth. These data suggest that inherited thrombophilia may play a role in the etiology of IVF failures. The differential antibiotic prophylaxis reduces the abortion rate but also lowers the risk for development retardation, premature birth and preeclampsia.

Female↗

[The role of endocrine factors in the pathogenesis of spontaneous abortion after IVF-ET].

There is large body of evidence to show that the risk of early pregnancy loss is higher after IVF-ET than after natural conception. Several hypotheses have been proposed to explain this phenomenon. One of the possible etiopathogetic factors is the patient's age which is significantly higher in women undergoing IVF than in the general population of naturally conceiving women. Immunologic factors have also been suggested. It seems that procedures like ICSI do not increase the risk of spontaneous abortion (SAB) after IVF-ET. Moreover, the proportion of products of conception with chromosomal aberration in cases of SAB following ICSI procedure is not elevated. Many authors point to the problem of iatrogenic luteal defect after IVF-ET. The use of luteal support after IVF-ET is widely recommended. Interestingly, firm evidence is lacking regarding the efficacy of progestagen or hCG supplementation on the risk of SAB after IVF-ET. However the issue of the effectiveness of progesterone support in decreasing the risk of SAB after ART procedures is far from being conclusively resolved--it deserves well planned, randomized studied to be performed.

Abortion, Spontaneous↗

Results and complications of IVF therapy.

This review attempts to discuss the current efficacy of in-vitro fertilization (IVF) treatment, factors influencing IVF success rates, and complications of IVF therapy. The livebirth rate per oocyte retrieval and per embryo transfer (ET) have been among the most widely used indices of success. To determine true efficacy, success rates have to be related to patient characteristics, such as age and cause of infertility. The cumulative conception rate after specified periods of treatment provides the most useful estimate of success rate after IVF. Approaches to further improving IVF treatment in the future are discussed. Considering the ongoing scientific research in the field of assisted reproduction, it should be the challenge of the nineties to further improve IVF success rates per treatment cycle by 50-100%.

Age Factors↗