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PubMed1998

In vitro and in vivo survival of frozen-thawed bovine oocytes after IVF, nuclear transfer, and parthenogenetic activation.

Cryopreservation of bovine oocytes would be beneficial both for nuclear transfer and for preservation efforts. The overall objective of this study was to evaluate the viability as well as the cryodamage to the nucleus vs. cytoplasm of bovine oocytes following freezing-thawing of oocytes at immature (GV) and matured (MII) stages using in vitro fertilization (IVF), parthenogenetic activation, or nuclear transfer assays. Oocytes were collected from slaughterhouse ovaries. Oocytes at the GV, MII, or MII but enucleated (MIIe) stages were cryopreserved in 5% (v/v) ethylene glycol; 6% (v/v) 1,2-propanediol; and 0.1-M sucrose in PBS supplemented with 20% (v/v) fetal bovine serum. Frozen-thawed oocytes were subjected to IVF, parthenogenetic activation, or nuclear transfer assays. Significantly fewer GV oocytes survived (i.e., remained morphologically intact during freezing-thawing) than did MII oocytes (47% vs. 84%). Subsequent development of the surviving frozen-thawed GV and MII oocytes was not different (58% and 60% cleavage development; 7% and 12% blastocyst development at Day 9, respectively, P > 0.05). Parthenogenetic activation of frozen-thawed oocytes resulted in significantly lower rates of blastocyst development for the GV than the MII oocyte groups (1% vs. 14%). Nuclear transfer with cytoplasts derived from frozen-thawed GV, MII, MIIe, and fresh-MII control oocytes resulted in 5%, 16%, 14%, and 17% blastocyst development, respectively. However, results of preliminary embryo transfer trials showed that fewer pregnancies were produced from cloned embryos derived from frozen oocytes or cytoplasts (9%, n = 11 embryos) than from fresh ones (19%, n = 21 embryos). Transfer of embryos derived by IVF from cryopreserved GV and MII oocytes also resulted in term development of calves. Our results showed that both GV and MII oocytes could survive freezing and were capable of developing into offspring following IVF or nuclear transfer. However, blastocyst development of frozen-thawed oocytes remains poorer than that of fresh oocytes, and our nuclear transfer assay suggests that this poorer development was likely caused by cryodamage to the oocyte cytoplasm as well as to the nucleus.

Animals↗
PubMed1999

Cell allocation and chromosomal complement of parthenogenetic and IVF bovine embryos.

Considerable concerns exist regarding the quality of parthenogenetically activated embryos in terms of sufficient numbers of cells comprising the inner cell mass (ICM) and trophectoderm (TE) and the ploidy. Therefore, these two parameters were used to assess the quality of embryos derived from parthenogenetic activation by using calcium ionophore A23187 (CaI) followed by either 6-dimethylaminopurine (6-DMAP, 3.5 hr or 6.5 hr) or cycloheximide (CHX) plus cytochalasin D (CD). The conventional in vitro (IVF) produced embryos served as a control. Double staining of the parthenogenetic blastocysts showed that the total cell number (TC) of embryos from the 6-DMAP 3.5 hr (87.0 +/- 5.3) and CHX+CD (79.0 +/- 6.1) groups was not different (P > 0.05), but was lower than that of control embryos (116.0 +/- 5.8, P < 0.001). The mean ratios of inner cell mass (ICM) and trophectoderm (TE) cells in the 6-DMAP 3.5 hr group (0.57 +/- 0.04) and the control IVF group (0.50 +/- 0. 02) did not differ significantly. Both were higher than those of the CHX+CD group (0.36 +/- 0.02; P < 0.05). Further analysis of chromosomal compositions of developing stage embryos at day four after IVF or parthenogenetic activation demonstrated that prolonged treatment with 6-DMAP for 6.5 hr resulted in a significantly lower percentage of diploid embryos and a significantly higher percentage of abnormal ploidy embryos compared to treatment with 6-DMAP for 3.5 hr or with CHX and IVF. In conclusion, parthenogenetic activation of bovine oocytes with CaI followed by 6-DMAP for 3.5 hr could produce better quality embryos in terms of total cell numbers, the number of cells allocated to the ICM, and the ploidy of embryos.

Adenine↗
PubMed2004

Integrated first- and second-trimester Down syndrome screening test among unaffected IVF pregnancies.

OBJECTIVE: The aim of the current study was to assess the profile of markers that constitute the integrated test and to measure its false-positive rates (FPR) among a preselected group of unaffected IVF pregnancies. These results were compared with the reference laboratory values that reflect the general obstetric population, which underwent the same investigative protocol. METHODS: Ninety-nine unaffected singletons from IVF-pregnant women and 1781 controls, all evaluated by the same laboratory, underwent a nondisclosure integrated Down syndrome screening test. This test comprised first-trimester nuchal translucency (NT) and pregnancy-associated plasma protein-A (PAPP-A) assessment, followed by a midgestation quadruple test. Only upon completion of the integrated screening test, the parturient women were informed of its results. RESULTS: The mean maternal age of the study and the control group was 32.2 +/- 4 and 30.4 +/- 4 years respectively (t-test <0.005). The marker levels were expressed as multiples of the gestation-specific normal medians. The IVF group had lower PAPP-A (0.78 vs 1.03, t-test P < 0.05) and higher NT (1.14 vs 1.01, t-test P < 0.05) values, respectively. All the other markers were similar for both groups. On the basis of the integrated test, a higher rate of IVF pregnancies were defined as being screen-positive (6.1% vs 3.7%), although the values did not reach a level of statistical significance. CONCLUSIONS: Since NT alone yielded the same FPR as the integrated test, the option of various sonographic screening combinations in this group warrants further investigation.

Chorionic Gonadotropin↗
PubMed1990

The value of hysteroscopy in elderly women prior to in vitro fertilization-embryo transfer (IVF-ET): a comparative study.

Two hundred eighty-four hysteroscopies were performed in 312 (91%) candidates for in vitro fertilization and embryo transfer (IVF-ET) who were divided into two groups. Group I consisted of elderly women over 40 years, and group II of women below this age. Although visualization revealed uterine abnormalities in 29.9% of all patients, abnormal findings were significantly increased in the former group in comparison to the latter (P less than 0.001). This difference was attributed mainly to uterine rather than cervical pathology. Furthermore, in elderly women age-related uterine pathology such as submucous myomata, endometrial hyperplasia, and polyps were more prominent, while in younger patients other uterine lesions such as adhesions and tubal ostia occlusion were more common. Moreover, treatment prior to IVF-ET resulted in 7 clinical pregnancies (8.9%) in group I and in 41 clinical pregnancies (19.9%) in group II, all of which failed in one to three cycles previously. It seems that hysteroscopic evaluation may reduce the IVF-ET failure rate due to intrauterine abnormalities in elderly as well as young patients, thus it becomes an absolute prerequisite for all patients scheduled for an IVF program.

Adult↗
PubMed1990

Comparison of singleton and multiple pregnancies in in vitro fertilization (IVF) and embryo transfer (ET).

The purpose of this study was to analyze factors associated with multiple gestations in IVF-ET. Twenty-seven multiple gestations conceived following IVF-ET resulted in the delivery of 20 sets of twins and three sets of triplets. One quadruplet pregnancy was terminated due to heavy bleeding. There were four "vanishing sacs," two of which resulted in a twin pregnancy and two in singletons. These were compared to 88 singleton IVF-ET gestations. The only significant difference found was the higher numbers of embryos transferred in the multiple gestation group. No difference was found between the two groups in diagnosis, stimulation protocol, estradiol, response, number of eggs, fertilization, and cleavage rate. Maternal age was younger in the multiple-gestation group, though not statistically significant. It is thus suggested that limitation of the number of embryos transferred is the only means to reduce the incidence of multiple gestations in IVF-ET.

Adult↗
PubMed1996

The initial flare-up induced by gonadotropin releasing hormone agonist may serve as a predictor of ovarian response in the current IVF-ET treatment cycle in normogonadotropic women aged 40-48 years.

OBJECTIVE: Our purpose was to assess the potential role of the baseline hormone profile in combination with the initial pattern of response to gonadotropin releasing hormone (GnRH) analogue in predicting ovarian function and hence reproductive outcome in normogonadotropic patients aged 40 years or older undergoing IVF treatment. PATIENTS AND METHODS: A retrospective analysis of 394 controlled ovarian hyperstimulation (COH) cycles that reached the stage of oocyte retrieval was conducted. The study included 163 normogonadotropic (serum FSH < or = 15 IUIL) patients aged between 40 and 48 years who had regular menstrual cycles. Superovulation was achieved using menotropins in combination with GnRH analog (short protocol, beginning on menstrual day 2). The ovarian response was monitored on the third cycle day, the day following the first GnRH analogue administration. RESULTS: Cycle distribution by patient age was 175 (44.4%), 122 (30.9%), and 97 (24.7%), while the patient distribution was 85 (52.2%), 48 (29.5%), and 30 (18.3%) for age groups 40-41, 42-43, and 44-48 years, respectively. The mean total dose of menotropins needed for optimal COH was 1787 IU (range, 600-6000 IU). This dose increased with age, while the yield of oocytes and embryos declined (P < 0.05; ANOVA). A positive correlation was demonstrated between the E2 level on day 3 (GnRH analogue flare effect) and the outcome of the treatment cycle (number of oocytes and embryos). Using multiple stepwise regression analysis, it was demonstrated that the initial (day 3) serum E2 levels, combined with baseline FSH levels, patients's age and body mass index enabled early prediction of the ovarian response in the current IVF-ET treatment cycle (oocytes = 8.2 - 0.18 x Age + 0.17 x BMI - 0.12 x FSH + 0.0042 x E2). CONCLUSIONS: Multiple-parameter analysis demonstrated that the use of the initial E2 response to GnRH analogue stimulation combined with basic clinical data may assist in the prediction of ovarian function and hence the reproductive outcome in normogonadotropic IVF patients aged 40 years or older. This may serve as a clinical tool for improving patient selection and treatment outcome in IVF-ET.

Adult↗
PubMed1996

Quality control in IVF with mouse bioassays: a four years' experience.

OBJECTIVE: We analyzed retrospectively the relevance of 4 years of quality control on homemade culture medium with the mouse IVF and zygote bioassay. DESIGN: In vitro or in vivo fertilized mouse oocytes were cultured in each batch of medium. Two-cell-stage and expanded blastocyst development was recorded for each batch of medium. Data on fertilization and embryo quality obtained in human in vitro fertilization were recorded for each batch. IVF treatment cycles for male infertility and cycles with sperm microinjection were excluded. RESULTS: Human oocyte fertilization dropped from 60 to 54%, respectively, from 57 to 41% in a significant way (P < 0.05 resp. P < 0.01) and the human mean embryo score decreased from 4.17 +/- 1.21 to 3.69 +/- 1.06 (P < 0.05) when media were used with a low two-cell-stage development (< or = 75%) for the mouse zygote or mouse IVF bioassay. The pregnancy rate was not affected. CONCLUSIONS: Media with high scores in mouse bioassays show higher fertilization rates and better embryo quality when used for human IVF.

Animals↗
PubMed1995

Cumulative birth rates following cryopreservation of all embryos in stimulated in vitro fertilization (IVF) cycles.

OBJECTIVE: To cryopreserve all good-quality embryos available after IVF is one way to avoid an impending hyperstimulation and a more attractive alternative to a couple than cancellation of the cycle. At Sahlgrenska University Hospital this method has been practiced since 1991. The aim of this study was to assess the success rate (defined as childbirth per couple) after IVF treatment including one stimulated cycle, resulting in cryopreservation of all good-quality embryos available, followed by replacement of frozen/thawed embryos in one or more natural cycles. DESIGN: A cohort of 32 women undergoing one stimulation for IVF between January 1991 and December 1993 where all good-quality embryos were cryopreserved and transferred in a later spontaneous cycle were studied retrospectively. The cumulative childbirth rate per couple was calculated. RESULTS: A total of 28 women underwent a total of 45 transfers with frozen-thawed embryos. In 4 women no transfer has taken place so far. The clinical pregnancy rate per embryo transfer was 33% (15/45) and per patient 54% (15/28). Three spontaneous abortions occurred giving a cumulative childbirth rate per patient of 39% (11/28). In addition, 6 out of the 28 women still have embryos left in the freezer. CONCLUSION: Cryopreservation of all good-quality embryos available after IVF is a highly effective alternative to cancellation of a cycle when there is impending hyperstimulation. The use of this approach results in a cumulative childbirth rate per couple of at least 39%. Since only one stimulation was performed, it also seems to be cost effective.

Abortion, Spontaneous↗
PubMed1995

Influence of follicular phase duration on human granulosa-luteal cell subpopulations in natural and stimulated IVF-ET cycles.

OBJECTIVES: To observe the granulosa-luteal cell subpopulations presented within follicular aspirates concerning duration of the follicular phase and the type of IVF protocol. DESIGN: Cells were obtained from dominant follicles of 40 women with natural IVF-ET cycles, in which preovulatory hCG was given when the follicle was mature, and from 40 follicles of 32 women with hMG and hCG stimulated IVF-ET cycles. Granulosa-luteal cell subpopulations were observed by computerized image analysis in which hCG was localized using immunoperoxidase staining. RESULTS: (1) The nonluteinized granulosa cells from natural developing follicles were larger than those from stimulated ones regardless of the follicular phase duration. (2) The size of each luteinized cell subpopulations was influenced neither by the two IVF protocols nor by the follicular phase duration. (3) The hCG stained cells from natural developing follicles were larger than the ones from stimulated follicles and their relative number in aspirates was higher. Cell areas and distribution were not influenced by the duration of follicular phase. (4) In stimulated conditions, hCG stained cells became larger if follicular phase was longer. CONCLUSIONS: Duration of the follicular phase influences the immunocytochemical hCG localization and the morphometric characteristics of granulosa-luteal cell subpopulations presented within natural developing follicles and stimulated ones.

Adult↗
PubMed1995

Use of follicle-stimulating hormone (FSH) to increase the in vitro fertilization (IVF) efficiency of mice.

PURPOSE: The possibility of increasing the efficiency of an in vitro fertilization system (IVF) for Swiss OF1 mice was studied. The experimental protocol proposed analyzed the use of FSH as a superovulatory inducing hormone in comparison to traditional PMSG treatment. At the same time, the quality of IVF-derived embryos was evaluated both in vitro, with culture in CZB medium and fixation in advanced stages of development, and in vivo, by transfer to female recipients. RESULTS: Treatment with FSH induced a much higher ovulation number compared PMSG (64.26 vs 33.85; P < 0.01). With this gonadotropin, IVF provided a positive tendency to normal fecundation (67.76 vs 64.72; P < 0.1) and a much lower index of abnormal division in embryos (10.57 vs 15.11; P < 0.05). The viability of embryos obtained from donors treated with hormones was similar, although differences did exist regarding embryo origin: those obtained following natural fertilization showed a higher developmental capacity from in vivo (P < 0.05) and in vivo (P < 0.05). CONCLUSIONS: We conclude that FSH is an improved superovulation alternative treatment in comparison to PMSG for IVF. It provides a higher number of embryos with the same in vitro and in vivo viability as those obtained from PMSG.

Animals↗
PubMed1994

Addition of a gonadotropin releasing hormone (GnRH) antagonist and exogenous gonadotropins to unstimulated in vitro fertilization (IVF) cycles: physiologic observations and preliminary experience.

PURPOSE: To describe our preliminary experience with the addition of a GnRH antagonist (Nal-Glu) and exogenous gonadotropins (follicle stimulating hormone; FSH) to unstimulated IVF cycles. METHOD: Seven spontaneously ovulatory women underwent eight unstimulated IVF cycles at our institution. They were treated with a single dose of Nal-Glu, 50 micrograms/kg, or with a combination of Nal-Glu, 50 micrograms/kg, and exogenous FSH, 150-300 IU, during the late follicular phase of spontaneous cycles. They then received 10,000 IU of human chorionic gonadotropin (hCG) to time accurately follicle aspiration in unstimulated IVF cycles. RESULTS: Two women underwent three cycles with Nal-Glu alone on the day of hCG administration. One pregnancy resulted. Five women underwent five cycles with 3 to 6 days of daily Nal-Glu and FSH. Four of these cycles resulted in aspiration after the FSH dose was increased to 300 IU. Nal-Glu and FSH allowed continued development of the dominant follicle without the occurrence of luteinizing hormone (LH) surge. CONCLUSIONS: (1) Nal-Glu alone given 18 hr prior to hCG did not interfere with continued follicle viability or with the attainment of pregnancy. (2) Simultaneous Nal-Glu and FSH allowed for continued growth and development of the dominant follicle without the occurrence of an LH surge. (3) This preliminary experience confirms the feasibility of this novel approach, which may ultimately enhance the efficacy of unstimulated IVF cycles by eliminating premature ovulation and maximizing control of gonadotropin delivery to the developing follicle.

Adult↗
PubMed1997

Sperm count in ejaculates and after sperm selection with discontinuous percoll gradient centrifugation technique, as a prognostic index of IVF outcome.

Success of IVF with low sperm count will depend on the retrieval of the maximum number of normal motile sperms, and this makes the selection of an appropriate technique critical. Various in vitro methods have been developed for selecting human sperm cells. Sperm selection using percoll gradient has been reported to yield upto 60% motile and morphologically normal spermatozoa from a normal semen sample. In this study, we have attempted to determine a possible relationship between sperm count in ejaculates before and after selection with percoll gradient centrifugation on one hand, and fertilization, cleavage and pregnancy rates in an IVF program on the other. With increased sperm count at the time of IVF treatment using selected sperm, we observed higher fertilization, cleavage and gestational rates. In conclusion, sperm concentration before and after selection with percoll may be considered a prognostic parameter for the determination of fertilization potential and pregnancy rates in an IVF program.

Cell Division↗
PubMed1998

The need to step up the gonadotropin dosage in the stimulation phase of IVF treatment predicts a poor outcome.

PURPOSE: It is a common practice to increase the gonadotropin dose during ovarian stimulation when the estradiol (E2) rise is found to be inadequate. The prognostic impact of the use of this step-up regimen on the outcome of the affected in vitro fertilization (IVF) cycle is the subject of this study. METHODS: This is a retrospective analysis of IVF cycles in a series of consecutive patients who required an increase in the gonadotropin dosage during the stimulation phase because of inadequate E2 rise. Controls consisted of patients in whom the dose was not increased. After 4 days of stimulation, the gonadotropin dosage was increased if E2 levels failed to rise by 70% every 2 days. Outcome was defined in terms of maximum E2 level, number of follicles at aspiration, number of oocytes obtained, fertility rate, and pregnancy rate and was compared in study and control patients. Pregnancy was defined by sonographic demonstration of cardiovascular activity. RESULTS: One hundred forty-five patients were analyzed. A step-up regimen was used in 35 patients (24.1%). Patients who required the step-up dosing had significantly lower peak E2 levels (1373 vs 1828 pg/ml; P < 0.005), fewer follicles measuring greater than 16 mm (7.2 vs 9.7; P < 0.003), and fewer oocytes recovered (8.3 vs 11.2; P < 0.009). The fertilization rate (67.6 vs 64.2%) was not significantly different. The pregnancy rate (8.5 vs 32.7%; P < 0.004) was significantly lower in the group requiring the step-up regimen. CONCLUSIONS: The utilization of a step-up regimen during an IVF treatment cycle is a predictor of a poor outcome for the specific IVF cycle. As this information is available before retrieval, consideration of cycle cancellation may be appropriate.

Adult↗
PubMed1998

Importance of endometrial quality in women with tubal infertility during a natural menstrual cycle for the outcome of IVF treatment.

PURPOSE: The importance of endometrial maturation at estimated time of implantation for the outcome of IVF treatment in regularly menstruating women with tubal infertility was evaluated. METHODS: FSH was measured on cycle day 3, on days 10-15 urine and blood were collected to estimate the day of the LH peak, and E2 and P4 were measured during the luteal phase, on cycle days 19-26. An endometrial biopsy was obtained on days LH + 3 to LH + 6. RESULTS: The number of subjects with delayed endometrial maturation was larger in the group of infertile women who did not become pregnant compared to pregnant women and controls. Those infertile women who did not become pregnant after IVF treatment also presented with a higher basal FSH on cycle day 3 and lower E2 and P4 AUC in the luteal phase. Six infertile women and two controls presented with mid- and late-proliferative endometrium in the luteal phase on cycle days LH + 3 to LH + 6, in the presence of adequate E2 and P4 secretion. Six morphological characteristics were compared in the three groups: (1) 17 infertile women who became pregnant, (2) 18 who did not become pregnant, and (3) 28 controls. The pregnant infertile women did not differ from the controls. The numbers of glandular and stromal mitoses were significantly higher in those women who did not become pregnant (P < 0.01) compared with those who became pregnant. Endometrial biopsies obtained on cycle days LH + 5 and LH + 6 showed significant differences in glandular epithelial height (P < 0.05) and number of vacuolated cells among the nonpregnant women (P < 0.01), the pregnant women (P < 0.05), and controls. CONCLUSIONS: A higher frequency of retarded endometrial development in women who did not become pregnant following IVF treatment was found. In some cases, endometrial insensitivity could most likely cause retarded endometrial development and failure of implantation after IVF treatment, which could not be overcome by routine luteal-phase support. However, our results do not allow conclusions concerning its relative importance compared to preembryo quality; this has to be investigated further.

Adult↗
PubMed2003

Pregnancy complications, obstetric risks, and neonatal outcome in singleton and twin pregnancies after GIFT and IVF.

PURPOSE: In vitro fertilization (IVF) and to a lower extent gamete intra-fallopian transfer (GIFT) have become routine infertility treatments in industrialized countries. Our purpose is to compare the obstetric and neonatal characteristics of singleton and twin pregnancies after GIFT and IVF with those conceived spontaneously. METHODS: This case-control study was conducted in a tertiary care medical center. The 322 singleton and 78 twin pregnancies after GIFT or IVF from 1991 through 1996 were evaluated and compared with each other, and with a control group that conceived spontaneously and matched for parity, maternal and gestational age. Statistical significance of differences was assessed by chi(2) test or two-tailed Fisher exact test. Continuous variables were compared by the paired t-test. RESULTS: Pregnancy-induced hypertension (PIH) and vaginal bleeding were significantly more frequent maternal complications in the GIFT/IVF singleton groups compared to controls. In twin pregnancies the rate of cesarean sections, vaginal bleeding and preterm labor were more common after GIFT/IVF but did not reach statistical significance. Assisted reproduction was associated with low birth weight only in twin pregnancies when controlled for confounding variables, however perinatal outcome was comparable. There was no significant difference in the outcome measures between GIFT and IVF pregnancies. CONCLUSION: After controlling for parity, maternal and gestational age, singleton pregnancies conceived by GIFT/IVF are at increased obstetrical risk, however the perinatal outcome is comparable despite a lower average birth weight.

Case-Control Studies↗
PubMed2005

Area under the curve for estradiol levels do not consistently reflect estradiol levels on the day of hCG administration in patients undergoing controlled ovarian hyperstimulation for IVF-ET.

PURPOSE: Most studies reported estradiol (E2) levels attained on day of hCG administration when investigating effect of E2 on IVF outcome. We studied whether a relationship exists between the area under the curve for E2 levels (AUC-E2) and E2 levels on hCG day during IVF-ET. METHODS: Retrospectively, we analyzed data for 313 patients who completed one IVF-ET cycle each. Patients were sorted according to AUC-E2 levels. Then we compared between each patient's own AUC-E2 and the corresponding E2 level on hCG day for the same patient. RESULTS: Although overall AUC-E2 correlated positively with E2 levels on hCG day, there was no consistent correlation between individual patients. CONCLUSIONS: AUC-E2 reflects more accurately the amount of E2 produced by the follicles during controlled ovarian hyperstimulation. The absence of a uniform correlation between AUC-E2 and E2 on hCG day may result in different conclusions when studying outcomes of IVF treatment.

Area Under Curve↗
PubMed2005

Single and repeated GnRH agonist stimulation tests compared with basal markers of ovarian reserve in the prediction of outcome in IVF.

PURPOSE: To study the value of a single or repeated GnRH agonist stimulation test (GAST) in predicting outcome in IVF compared to basal ovarian reserve tests. METHODS: A total of 57 women was included. In a cycle prior to the IVF treatment, on day 3, an antral follicle count (AFC) was performed and blood taken for basal FSH, inhibin B and E2 measurements, followed by a subcutaneous injection of 100 microg triptorelin for the purpose of the GAST. Twenty-four hours later blood sampling was repeated. All the tests were repeated in a subsequent cycle. From the GAST E2 and inhibin B response were used as test parameters. The outcome measures were poor ovarian response and ongoing pregnancy. Group comparisons were done using the Mann-Whitney or chi-square test. Univariate and multivariate logistic regression was applied to assess which test revealed the highest predictive accuracy as expressed in the area under receiver-operating characteristic curve (ROC(AUC)). Clinical value was compared by calculating classical test characteristics for the best logistic models. RESULTS: All the basal and GAST variables were significantly different in the poor responders (n = 19) compared to normal responders (n = 38). In the univariate analysis on cycle 1 tests the AFC was the best predictor for poor ovarian response, while in cycle 2 the E2 response in the GAST performed best (ROC(AUC) of 0.91 for both). Multivariate analysis of the basal variables led to the selection of AFC and inhibin B in cycle 1, yielding a ROC(AUC) of 0.96. Mean E2 response was selected in a multivariate analysis of the repeated GAST variables (ROC(AUC) 0.91). At a specificity level of -0.90, several logistic models including GAST variables appeared to have a sensitivity (-0.80), positive predictive value (-0.82) and false positive rate (-0.18), comparable to a logistic model containing AFC and inhibin B. None of the test variables showed a significant relation with ongoing pregnancy. CONCLUSIONS: The GAST has a rather good ability to predict poor response in IVF. However, comparing the predictive accuracy and clinical value of the GAST with a day 3 AFC and inhibin B, it appeared that neither a single nor a repeated GAST performed better. In addition, the predictive ability towards ongoing pregnancy is poor. Therefore, the use of the GAST as a predictor of outcome in IVF should not be advocated.

Adult↗
PubMed2006

Is intravenous immunoglobulins (IVIG) efficacious in early pregnancy failure? A critical review and meta-analysis for patients who fail in vitro fertilization and embryo transfer (IVF).

PROBLEM: Intravenous Immunoglobulins (IVIG) are widely used off label in the treatment of early reproductive failure. As IVIG is expensive, and may have side-effects, evidence of efficacy is needed. Previous results have suggested that the pre-conception treatment of primary recurrent abortion patients might be effective, but the data set has been too small for adequate statistical power. More recently it has been suggested that IVIG may improve the success rate of in vitro fertilization and embryo transfer (IVF) in patients with prior IVF failures, but clinical trials have given conflicting results that need explanation. Systematic reviews generating inconclusive results have focused on methodological rigor to the exclusion of biological plausibility. METHODS: Review of current basic science of design, measurement, and evaluation of clinical trials and basic science mechanisms providing a rationale for treatment. Meta-analysis of published randomized controlled and cohort-controlled trials (updated with two unpublished data sets) evaluating IVIG treatment in IVF failure patients. Live birth rate was used as the most relevant endpoint. The ability of different sources of IVIG to suppress natural killer (NK) cell activity was determined using a standard (51)Cr-release assay in vitro. RESULTS AND CONCLUSIONS: Meta-analysis of three published randomized controlled trials (RCTs) of IVIG in IVF failure patients shows a significant increase in the live birth rate per woman (p = 0.012; Number Needed to Treat for 1 additional live birth, NNT = 6.0 women). Using live birth rate per embryo transferred, and adding data from two cohort-controlled trials to the meta-analysis further supports this conclusion (overall p = 0.000015, NNT = 3.7 women). Relevant variables appear to include properties and scheduling of the IVIG, and selection of patients with abnormal immune test results. Different IVIG preparations vary significantly in their ability to suppress NK activity in vitro. A rationale for use of IVIG is provided by a review of mechanisms of IVIG action and mechanisms underlying failure of chromosomally normal embryos.

Adult↗