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Seasonal influences on in vitro fertilization and embryo transfer.

PURPOSE: The study was aimed to investigate the influence of time factors (day, week, month) on pregnancy rates and in vitro fertilization (IVF) and embryo transfer (ET) parameters. METHODS: 8,184 IVF-ET cycles, taking place in two IVF centers from 1992 to 1999, were analyzed. Multiple logistic and linear regression methods were performed as statistical analyses. RESULTS: Oocyte pickup on Tuesdays achieved a significantly higher mean number of oocytes (median: 7) and the highest pregnancy rate (PR) (33.4%) per ET There was a significant variation over the year, with the lowest PR/ET in July (25.71%) and the highest in December (35.5%). Concerning outcomes, the age factor and the number of embryos transferred had the highest significant (p < 0.0001) influence. CONCLUSIONS: The observed weekly rhythm for oocyte pick-ups is certainly due to preprogrammed ovarian stimulation used in our IVF programs. Age as well as the number of embryos transferred are the main influencing factors on a positive outcome and more predictive than seasonal aspects.

Adult↗

Changes in CA602 and CA546 concentrations in patients during in-vitro fertilization and embryo transfer, and ovarian hyperstimulation syndrome.

Changes in CA602 and CA546, two carbohydrate-related antigens newly established in our institute, were evaluated during the course of in-vitro fertilization and embryo transfer. The concentration of CA602, an antigen with characteristics similar to those of CA125, did not change substantially until embryo transfer. In patients with clinical evidence of ovarian hyperstimulation syndrome (OHSS), a significant increase in serum concentrations of CA602 was observed 10 days after embryo transfer (P < 0.01). There were no significant changes in the patients without OHSS. A significant elevation of oestradiol concentration in OHSS patients was also observed, with the variation before oocyte retrieval being greater than that seen with CA602. The concentration of CA546, which had lower false-positive rates in benign disease, did not differ significantly in the OHSS and non-OHSS patients. Our data demonstrate that serum concentrations of CA602 are increased even in early stages of OHSS, and suggest a possible role for this antigen as a marker for OHSS.

Adult↗

Effects of low-dose human chorionic gonadotropin on corpus luteum function after embryo transfer.

This paper reports the effect of low-dose human chorionic gonadotropin (hCG) on the levels of serum hCG, progesterone, and estradiol, luteal-phase length, and conception in 20 patients undergoing in vitro fertilization and embryo transfer (IVF-ET). Alternate patients in a group of 20 received 1000 IU hCG on the day of embryo transfer and 3 days after. Six and 9 days from embryo transfer 2000 IU hCG was given. The remaining patients served as controls. No patients in the treated group and four in the control group became pregnant. The endocrine profiles with respect to hCG, progesterone, and estradiol levels were similar in the treated patients compared with pregnant patients in the control group. Treated patients had significantly longer (18.0 +/- 1.1 days) luteal phases compared with nonpregnant patients in the control group (12.5 +/- 1.2 days), indicating that low-dose hCG prolonged the life of the corpus luteum. It was concluded that while the administration of low-dose hCG prolonged the life of the corpus luteum, it did not apparently improve the conception rate.

Chorionic Gonadotropin↗

Effects of embryo transfer and cortical ectopias upon the behavior of BXSB-Yaa and BXSB-Yaa + mice.

The BXSB-Yaa and BXSB-Yaa + inbred strains of mice differ primarily with respect to the Y chromosome, although there is evidence that they differ on several autosomal genes as well. Each strain has ectopic collections of neurons in neocortical layer I (ectopias), with a higher occurrence in males (58%) than females (42%). Conventionally reared mice from these strains were compared to mice that were transferred, as 8-cell embryos, into the uteri of non-autoimmune recipients, who gave birth to and reared the offspring. The transfer procedure did not change the incidence of ectopias in either sex. There were, however, major differences in behavior. Compared to conventionally reared controls, embryo transfer mice had greater behavioral asymmetry, poorer performance in a black-white discrimination, poorer Morris maze learning, better Lashley maze learning, and better performance in a two-way shuttlebox. Within the transfer groups, females differed as much as males, confirming our prior findings and supporting our thesis that the two strains differ on several autosomal genes in addition to the Y chromosome. These findings show that the intra-uterine environment can powerfully and selectively affect later behavior. When ectopic and non-ectopic mice were compared, BXSB-Yaa mice with neocortical ectopias were better able to learn the Morris spatial maze than non-ectopic controls; this was true whether the mice were conventionally reared or embryo transferred. In contrast, BXSB-Yaa + ectopic mice did not differ from their controls if conventionally reared, but were much worse than controls if embryo transferred.

Animals↗

In vitro simulations of embryo transfer in a laboratory model of the uterus.

Embryo transfer (ET) is the final manual intervention during which the newly formed embryo is placed within the uterus by a transcervical catheter. The loading of the syringe-catheter complex with the transferred volume consists of the transfer media (which contains the embryos) separated by air spaces on both sides. The dynamics involved in injecting the syringe-catheter complex is not well understood nor has it been investigated to date. We developed an in vitro experimental setup for simulations of ET into a rigid transparent uterine model. The catheter was loaded in sequences of liquid and air as it is in the clinical setting. The transferred liquid was colored with a dye and its dispersion within the uterine cavity was recorded by a video camera. The results demonstrated, for the first time, the importance of having a gas phase in the catheter load. The resulting air bubbles within the uterus were carried upward towards the fundus by buoyant forces, thereby dragging behind them the transferred liquid which contained the embryos. This could be expected to substantially increase the probability for the embryos to be present near the fundal wall at the time window for implantation. There was also evidence of a dependency of the rate of injection upon the catheter load into the uterus: a low speed generated several air bubbles which led to more of the transferred liquid being carried towards the fundal end, thus possibly enhancing the potential for implantation.

Embryo Transfer↗

Follicular fluid steroid content and in vitro steroid secretion by granulosa-lutein cells from individual follicles among different stimulation protocols for in vitro fertilization-embryo transfer.

The in vitro steroidogenic capacity of granulosa-lutein (G-L) cells aspirated from individual follicles during cycles of in vitro fertilization-embryo transfer was examined and compared among three different stimulation protocols: human menopausal gonadotropins (hMG), clomiphene citrate (CC) and hMG, and follicle stimulating hormone (FSH). In addition, the clinical outcome of the patients in each protocol was examined. After 3 days of culture in basal medium, fresh medium with or without androstenedione (A) (10(-7) M) was added for 24 hr, at which time medium was obtained for measurement of progesterone (P) and estradiol (E) content. Follicular fluid (FF) P, E, and A were measured in each follicle and compared among protocols. FF from individual follicles in patients stimulated with FSH contained higher levels of P compared to FF from patients stimulated with hMG or CC/hMG, while E was higher in patients stimulated with CC/hMG compared to FSH or hMG. FF levels of A were not significantly different among the protocols. In vitro steroid secretion revealed a progressive increase in P secretion in contrast to decreasing E secretion when one compares CC/hMG, hMG, and FSH. Patients undergoing ovarian hyperstimulation with FSH had significantly more atretic oocytes identified at the time of oocyte harvest compared to patients undergoing ovarian hyperstimulation with CC/hMG or hMG. The hMG protocol yielded significantly fewer fertilized oocytes, cleaved embryos, and transferred embryos, compared to the CC/hMG and FSH protocol, however, there was no significant difference in pregnancy rate among the three protocols. These data demonstrate that individual follicles contain G-L cells with markedly different abilities to luteinize in vitro as assessed by steroid secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗

Endometrial thickness and volume by three-dimensional ultrasound one week after embryo transfer to detect pregnancy.

PURPOSE: Determine if the evaluation of endometrium one week after embryo transfer can predict pregnancy. METHODS: Endometrial volume and thickness were evaluated by three-dimensional ultrasound in 40 patients one week after embryo transfer. These results were compared to serum pregnancy test performed one week later. RESULTS: Twenty two patients have achieved pregnancy. A significant difference was found for endometrial volume: 6.49+/-1.97 mL vs. 3.40+/-1.11 mL (pregnant vs. not pregnant); and thickness: 11.15+/-2.75 mm vs. 9.77+/-1.85 mm. The ROC curve was used to detect the best cutoff values: endometrial volume of 3.48 mL (sensitivity-100%, specificity-68.2%) and endometrial thickness of 10.3 mm (sensitivity-72.2%, specificity-77.3%). The area under curve was significant higher for endometrial volume (0.909 vs. 0.745, P=0.027). No pregnancy was achieved in women who had an endometrial volume <3.8 mL (15 patients) or thickness < 7.9 mm (3 patients). CONCLUSIONS: The endometrial volume and thickness were significant higher in pregnant women and this difference was more prominent for endometrial volume.

Adult↗

[An application of in vitro fertilization--embryo culture--embryo transfer system on the drug safety evaluation: fertility test of male mice administered with the anticancer drug].

We examined an application of in vitro fertilization--embryo culture--embryo transfer system for reproductive and developmental study on the drug safety evaluation in mice. The male mice at 10 weeks of age were administered intravenously with a single dose of 75 mg/kg of the anticancer platinum complex (DWA 2114R) which inhibits DNA synthesis. Four to six weeks after administration, the males were mated with the superovulated females. Fertilization rates were significantly lower than the controls at each weeks after the administration. Furthermore, delayed formation of pronucleus was observed as compared with the control. Four weeks after administration, the preimplantation development to blastocyst stage of those embryos in vitro and the survival rates on the day 17 of gestation after embryo transfer suggested that a DNA synthesis in germ cells during maturation was inhibited and/or prevented by DWA 2114R. The results of in vitro fertilization reflected its sperm concentration rather than the administration of DWA 2114R. Thus, an analysis of the delayed formation of pronucleus observed fertilization in vivo could not done in detail. To use for the drug safety evaluation, there exist plenty of room for improvement in this system. These results have showed that the embryo culture and the embryo transfer are useful techniques as the reproductive and developmental study on the drug safety evaluation. These techniques bring additional informations on the pre- and post-implantation development in vivo.

Animals↗

Would legislation imposing single embryo transfer be a feasible way to reduce the rate of multiple pregnancies after IVF treatment?

Due to increased maternal and fetal risks, there is a strong opinion in favor of single embryo transfer (SET) in order to reduce the high multiple pregnancy rate after IVF. We have evaluated the effects on pregnancy rate and twinning of recent Swedish legislation on SET. The study comprised three embryo transfer (ET) periods: period I, autumn 2001-spring 2002 (n=609), with a double embryo transfer (DET) policy; period II, autumn 2002 (n=320), a transitional period; and period III, January-September 2003 (n=433), with a SET policy. During the three periods, the SET rates were 25.1, 55.5 and 72.7%, respectively (Kruskal-Wallis test P<0.0001). There was no difference in clinical pregnancy rates (33.3, 32.8 and 37.4%, respectively) (P=0.4), but the twinning rate was significantly lower in the third period (6.2 versus 22.6% in period I and 16.3% in period II) (P<0.005). After introducing a SET policy, the expected decline of twinning was met at an unchanged clinical pregnancy rate. Thus, the SET legislation had no negative consequences for the couples. On the contrary, the lower rate of twinning is expected to reduce the severity and rate of pregnancy complications after IVF. Whether legislation or voluntary SET is the most feasible way to proceed, in order to reduce the multiple pregnancy rates after IVF, can be debated.

Adult↗

Evaluation of Crestar, a synthetic progestogen regime, for synchronising oestrus in maiden heifers used as recipients of embryo transfers.

Crestar consists of an ear implant containing 3 mg norgestomet combined with an intramuscular injection of 3 mg norgestomet and 5 mg oestradiol valerate. Its effectiveness for synchronising oestrus in embryo transfer recipients was evaluated in comparison with a progesterone-releasing intravaginal device (PRID) and prostaglandin regimen, using 334 maiden heifers. The treatment devices were inserted on day 1, prostaglandin was administered to the PRID-treated heifers on day 8 and the devices were removed on day 10. High proportions of the heifers were seen in oestrus within five days of the removal of the devices after both the PRID prostaglandin (90.4 per cent) and Crestar (86.2 per cent) treatments. The interval from the removal of the device to the onset of oestrus was significantly shorter for Crestar than for PRID prostaglandin-treated heifers (45 vs 51 hours, P < 0.001), and the duration of oestrus was significantly longer (13 vs 10 hours, P < 0.01). The PRID prostaglandin treatment resulted in a higher degree of synchrony than the Crestar treatment (74.1 per cent vs 61.8 per cent, P < 0.05). There were no significant differences between the treatments in the proportions of the heifers selected as embryo transfer recipients or in the proportions which became pregnant after embryo transfer.

Animals↗

[Timing of embryo transfer and success of pregnancy in the human].

The best moment for human embryo transfer has not yet been accurately determined. The human uterus is able to receive young embryos (2, 4 cell-stage and even pronucleated eggs), insure their growth and implantation at a rate that does not exceed, however, 15% for one transferred egg. At the present time in vitro culture to the blastocyst stage, which impairs human embryo viability, should be avoided. Contrary to classical IVF, it becomes possible to dissociate embryo and endometrial ages when transferring frozen-thawed eggs. Our study concerns 443 spontaneous, stimulated or artificial cycles, performed in patients with normal or without endogenous ovarian function (tabl. 1). There was trend towards enhanced pregnancy rates (17%) for synchronous as compared to one-day asynchronous transfers (9%) (tabl. 2). Similar data, widely stated in mammals, emphasize the necessity of a precise chronology of embryo transfer. Embryos only survive and get implanted when placed in a receptive uterus. The onset of the refractory period appears to be closely linked to the maternal steroid environment. Consequently, no pregnancies arose from transfer of donated embryos beyond 6 days of progestative supply in women deprived of endogenous ovarian function. In the same way, administration of progesterone 40 h before oocyte recovery seemed to advance the refractory phase. Indeed, a reduction in the pregnancy rate per transfer was observed in such circumstances without any obvious impairment of embryo viability (tabl. 4). The best pregnancy rate was obtained in synchronous transfers while a one-day disynchronization reduced this rate by half.

Animals↗

The successful use of pronuclear embryo transfers the day following oocyte retrieval.

A retrospective analysis of results from 114 initiated in-vitro fertilization cycles utilizing pronuclear embryo transfer is presented. Patients were unselected for age or infertility criteria, constituted a continuous series and were grouped according to response to stimulation (Group 1, ideal; Group 2, suboptimal) or ovarian reserve (Group 3, poor). At 16-18 h post-insemination, embryos were scored for alignment of pronuclei and nucleoli and the appearance of the cytoplasm, generating an embryo score (ES). Transfers were performed 24-26 h post-insemination using two to six embryos with the highest ES. A corrected score was calculated (total score/number of embryos; CS). A total of 114 initiated cycles resulted in 97 oocyte retrievals with 38 clinical pregnancies (39%; 15% implantation). Pregnancy rates were significantly different between the three groups; 37 pregnancies in Group 1 (55% clinical pregnancy; 20% implantation), none in Group 2 and one in Group 3 (6%; 2% implantation: P < 0.001). The ES of transferred embryos correlated with groups. There was a strong correlation between CS and implantation and delivery rates. CS >15 resulted in a 28% implantation; 65% delivery rate. CS <14 resulted in four pregnancies, one delivered. The data show that oocyte quality and pronuclear embryo morphology are related to implantation and that pronuclear embryos can be successfully selected for embryo transfer.

Abortion, Spontaneous↗

The embryo versus endometrium controversy revisited as it relates to predicting pregnancy outcome in in-vitro fertilization-embryo transfer cycles.

To evaluate embryonic and endometrial factors for their value in predicting pregnancy outcome in in-vitro fertilization (IVF) and embryo transfer, a retrospective data collection and prospective uterine artery colour Doppler imaging study was performed in a university-based IVF-embryo transfer programme setting. A total of 210 patients were included and grouped as follows: (I) IVF with controlled ovarian stimulation (214 cycles); (II) frozen-thaw cycle of autologous embryos (30 cycles); (III) oocyte donation, no cryopreservation (12 cycles); (IV) frozen-thaw cycle with embryos from donated oocytes (10 cycles). Embryo quality was significantly better in pregnant than non-pregnant cycles (group I, P = 0.0104; groups II-IV, P = 0.0418). The endometrial echo was significantly thicker in pregnant versus non-pregnant patients in group I (P = 0.0059), but not in groups II-IV (P = 0.741). Past uterine surgery or abnormalities had no effect on pregnancy outcome. There were no significant differences in mean uterine artery resistance index or peak systolic velocity in pregnant versus non-pregnant patients in groups II-IV. Thus, embryo quality is the most reliable predictor of pregnancy outcome. Endometrial measurements were significantly thicker in subsequently pregnant patients only in group I, where the endometrium reflects the hormonal environment. Doppler parameters were not useful in predicting pregnancy outcome.

Arteries↗

Marked improvement in clinical pregnancy rates following in vitro fertilization-embryo transfer seen when transfer technique and catheter were changed.

PURPOSE: To compare in vitro fertilization (IVF) outcome with two different embryo transfer (ET) catheters: the Frydman and Wallace catheters. METHODS: Retrospective review of outcome of IVF cycles where there was at least one embryo that had assisted hatching prior to transfer at 72 hours according to which catheter was used. RESULTS: Pregnancy rate 17.6% per transfer with Frydman (FET-SET) vs 44.2% for fresh ETs and 15.4% and 43.2% for frozen ETs. The implantation rates for fresh ETs were 7.6% vs 20.0% for fresh and 5.7 vs 21.1% for frozen ETs. CONCLUSION: The soft Wallace catheter is superior to the stiffer Frydman catheter when transferring embryos subjected to assisted embryo hatching.

Catheterization↗

Analysis of intra-uterine cytokine concentration and matrix-metalloproteinase activity in women with recurrent failed embryo transfer.

BACKGROUND: In all IVF programmes, some patients fail to achieve an ongoing pregnancy, even after numerous embryo transfer procedures. An unfavourable environment within the uterus might be a contributory factor to such recurrent implantation failure. This question was addressed by measuring cytokine concentrations and matrix metalloproteinase activities in fluid derived from uterine irrigation of such patients. METHODS AND RESULTS: The uterine cavities of 22 patients who had previously undergone embryo transfer of at least 10 embryos without ongoing pregnancy were irrigated during the luteal phase. The resultant fluid was assayed for the concentration of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, leukaemia inhibitory factor (LIF), IL-10 and matrix metalloproteinase (MMP) -2 and -9 activity. The results were compared with those of a control population of women known to be previously fertile (n = 16) and also with women with recurrent spontaneous abortion (n = 13). In the recurrent implantation failure group, the MMP score and IL-1beta concentration were significantly higher than those in the control group, whereas concentrations of IFN-gamma and IL-10 were significantly lower. CONCLUSIONS: In IVF patients with recurrent implantation failure, an altered pattern of intra-uterine cytokine concentration and MMP activity was observed.

Abortion, Habitual↗

[Analysis of factors influencing the clinical in a frozen thawed embryo transfer program].

OBJECTIVE: To analyze the factors influencing the outcome in a frozen thawed embryo transfer (FTET) program. METHODS: Sixty FTET cycles performed in 53 cases from September 1997 to May 2000 were analyzed retrospectively. The related parameters were compared between the conceived and non-conceived cycles. RESULTS: One hundred and seventy eight out of 252 thawed embryos were survival. Embryo transfers were undergone in 57 cycles (53 patients), resulting in 17 pregnancies (30% per transfer or 28% per thawed cycle). There were no significant difference between conceived and non-conceived cycles in terms of the controlled ovarian hyperstimulation protocols, numbers of developed follicle and oocyte retrieved, fertilization rate, numbers of frozen embryo and the luteinizing hormone, estradiol, progesterone levels on human chorionic gonadotropin triggering day. The percentage of good quality embryo before freezing and after thawing and survival thawed embryos were higher in conceived cycles than those in non-conceived cycles (83.8% Vs 60.7%, 76.8% Vs 50.0%, 82.4% Vs 66.3%, respectively P < 0.05). CONCLUSIONS: Good quality of frozen-thawed embryos and the trilaminar sonographic pattern of endometrium may be reliable predictors of success in pregnancy.

Cryopreservation↗

Transfallopian tube embryo transfer: successful pregnancy outcome.

A case of partial Asherman syndrome and blocked fallopian tube following complication of cesarean section is presented. Two IVF-ET attempts failed where difficulty at uterine embryo transfer was encountered. Transtubal embryos transferred 48 hr after transvaginal oocyte collection and in vitro fertilization resulted in an in utero pregnancy and delivery.

Adult↗

Comparable implantation rates with fresh vs frozen embryo transfer suggests that controlled ovarian hyperstimulation has an adverse effect on conception outcome.

PURPOSE: A retrospective comparison of fresh vs frozen embryo pregnancy rates. METHODS: All frozen embryos transferred used in the analysis including deselected embryos from the oocyte retrieval cycle, and twice-frozen embryos. RESULTS: Pregnancy and implantation rates following fresh or frozen embryo transfers were similar. CONCLUSION: The similar outcomes despite the obvious disadvantages for the frozen-thawed embryo suggests that some other factor reduces the chance of embryo implantation on oocyte-retrieval cycles. An adverse affect of controlled ovarian hyperstimulation on the uterine environment is a strong possibility.

Adult↗