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Impact of intramural leiomyomata on in-vitro fertilization-embryo transfer cycle outcome.

PURPOSE OF REVIEW: The effect of leiomyomata on implantation and pregnancy rates resulting from in-vitro fertilization-embryo transfer has not been clearly defined. Submucosal and intramural leiomyomata which distort the endometrial cavity clearly affect outcome. However, the impact and possible mechanism of action of intramural lesions, which do not clearly alter the contour of the endometrial cavity, remain controversial. This review evaluates recent literature addressing these issues. RECENT FINDINGS: Several recent studies have evaluated the impact of leiomyomata on the uterine environment. Alterations in uterine artery blood flow may have an impact on implantation, although conflicting results have been reported. Other recent studies have evaluated alterations in gene expression and local cytokine release which may also play a role. Five recently published clinical case-controlled trials provide conflicting information regarding the impact of these lesions on in-vitro fertilization-embryo transfer cycle outcome as measured by clinical pregnancy and implantation rates. Results varied from no effect to a highly significant and deleterious impact on cycle outcomes. These differences may be partly attributable to differences in patient inclusion criteria and inconsistencies in analyses of precise fibroid location and size. SUMMARY: Intramural leiomyomata, which impinge upon the uterine cavity, negatively affect in-vitro fertilization-embryo transfer cycle outcome. Myomectomy should be beneficial in these circumstances despite an absence of data in this regard. No definitive statements can be made regarding intramural leiomyomata, which do not distort the cavity due to differing outcomes from currently available investigations. In the absence of more clear cut data, no recommendation can be made to support routine myomectomy in these cases. Rather, clinical management should be individualized.

Embryo Implantation↗

Junctional zone contractions and embryo transfer: is it safe to use a tenaculum?

Applying a tenaculum to the cervix is a common practice when the correction of uterine position prior to embryo transfer is required. Our study was designed to assess junctional zone contractility before and after this procedure in 20 patients at the time of mock embryo transfer (mid-luteal phase, at commencement of down-regulation). Real-time transvaginal ultrasound and computer technology was used to evaluate the contraction pattern and frequency. When a tenaculum was applied, the total number of contractions, the number of cervico-fundal, random and opposing contractions all increased significantly (P values 0.0003, 0.005, 0. 001 and 0.007 respectively). Eleven women displayed cervico-fundal contractions, prominent opposing and random contractions were observed in all 20 patients and four patients generated fundo-cervical waves not seen in any case before stimulation with the instrument. In conclusion, manipulation with a tenaculum in the cervical area stimulates junctional zone contractions and is best avoided at the time of embryo transfer.

Cervix Uteri↗

Effect of timing of progesterone administration on pregnancy rate after embryo transfer in ovariectomized mares.

Ovariectomized recipient mares were divided into two groups. Group A mares received 300 mg progesterone in oil i.m. daily starting 5 days before transfer of a 7-day embryo. Group B mares received the same dose of progesterone, but starting at least 4 days before donor ovulation. Presence of an embryonic vesicle was determined by ultrasonography; mares were considered to be pregnant if they had normal vesicle development to Day 18. Pregnancy rates were: Group A, 6/8; Group B, 1/12 (P less than 0.01). An additional 4 mares in Group B had a vesicle visible at 14 days which degenerated or did not grow. These results indicate that, for establishment of pregnancy after embryo transfer, there is a need for synchrony of donor ovulation with onset of progesterone administration to ovariectomized recipient mares.

Animals↗

Blastocyst versus early cleavage embryo transfer: a retrospective analysis of 4,165 transfers.

PURPOSE: To compare the clinical outcomes after the transfer of blastocysts versus early cleavage embryos in assisted reproduction technologies (ART). METHODS: A retrospective analysis of all the ovarian stimulation-in vitro fertilization-embryo transfer cycles performed at the Centre for Human Reproduction, Athens, Greece, between June 1997 and December 2001. RESULTS: The number of blastocysts transferred per ET was significantly lower compared to that of all early cleavage embryos. The implantation rate of blastocysts was significantly higher compared to that of all other modes of transfer. Clinical pregnancy rate after the transfer of blastocysts was significantly increased compared to that after transfer of any early cleavage embryo. The viable pregnancy rate after the transfer of blastocysts was significantly increased only compared to that after the transfer of day-2 embryos. There were no significant differences regarding the multiple gestation rates among the various modes of transfer. CONCLUSION: The use of blastocysts in ART is beneficial when compared to that of day-2 embryos and at least comparable to that of day-3 embryos. Blastocyst culture and transfer remains a favourable and promising option in ART.

Adult↗

The outcome of in vitro fertilization and embryo transfer in women with polycystic ovary syndrome failing to conceive after ovulation induction with exogenous gonadotropins.

OBJECTIVE: To assess the outcome of in vitro fertilization and embryo transfer (IVF-ET) in women with refractory polycystic ovarian syndrome (PCOS). DESIGN: Retrospective case series with an age-matched control group. SETTING: Ovulation induction and IVF programs in a tertiary referral center. PATIENTS AND INTERVENTIONS: Nine patients with PCOS who failed standard ovulation induction treatment (clomiphene citrate plus greater than or equal to 6 ovulatory human menopausal gonadotropin [hMG] cycles) underwent 19 cycles of IVF-ET. Forty age-matched tubal factor patients who completed 40 cycles of IVF-ET served as a control group. OUTCOME MEASURES: Demographic features and IVF-ET cycle characteristics were compared using Student's t-test and Fisher's exact test. RESULTS: Cycles of IVF-ET in patients with PCOS were associated with higher estradiol levels (5,222 versus 4,009 pmol/L), lower hMG requirements (15.8 versus 19.6 vials), greater numbers of oocytes (7.6 versus 5.6), and lower fertilization rates (56% versus 75%) compared with tubal factor cycles (P less than 0.05). However, the number of embryos transferred (3.9 versus 4.0) and the clinical pregnancy rate per embryo transfer (24% versus 25%) did not differ significantly between the two groups. CONCLUSION: These results suggest that conception failure after six or more ovulatory hMG cycles in patients with PCOS does not adversely affect subsequent IVF performance.

Adult↗

[Influence of advanced age on the outcome of in vitro fertilization and embryo transfer].

OBJECTIVE: To determine the influence of age on the outcome of In vitro fertilization and embryo transfer (IVF-ET). METHODS: A retrospective study of 139 cycles of conventional IVF and 69 intracytoplasmic sperm injection (ICSI) cycles was performed between January 1999 and December 1999. RESULTS: A total of 208 patients (age 36 to 45 years) after IVF or ICSI were divided into five age groups (36 years group, n = 78; 37 years group, n = 49; 38 years group, n = 50; 39 years group, n = 18; 40 approximately 45 years group, n = 13). Pregnancy rate is 23.1%. There appear to be no significant difference between infertility duration, IVF cycles, fertilization rate and cleavage rate, the number and the quality of embryos transferred, and the prenatal outcome in each age group. But with the age growing, the number of follicles in each group decreased significantly (14.7 +/- 1.2, 13.0 +/- 2.0, 11.3 +/- 0.9, 9.7 +/- 0.9 and 6.5 +/- 1.9 respectively), the pregnancy rate were significantly lower (24.1, 20.5, 13.2, 11.1 and 9.8% respectively), implantation rate were significantly lower too (15.6, 11.2, 10.5, 6.5 and 2.2% respectively). But the abortion rate increase significantly (23.0, 27.2, 33.4, 41.2 and 43.3% respectively), and multiple pregnancy rate decreased (31.2, 27.3, 15.4, 6.7 and 0.0% respectively). The pregnancy rates of the ICSI and IVF were similar after stratification by age. CONCLUSIONS: The fecundity reduct significantly at the age older than 36 years old. It reduct more obviously when the age older than 40 years old. Transferring four or more embryos may increase pregnancy rate, but without increasing multiple pregnancy in women older than 40 years.

Adult↗

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↗

Primary ovarian pregnancy after donor embryo transfer: early diagnosis and laparoscopic treatment.

Primary ovarian pregnancy is a rare type of ectopic pregnancy, particularly following in vitro fertilization. Although there have been a few reported cases of primary ovarian pregnancy following in vitro fertilization embryo transfer, we believe this is the first report involving donor embryo transfer. A high index of clinical suspicion, abnormal human chorionic gonadotropin levels, and early ultrasound evaluation may aid timely diagnosis and appropriate management. This report provides a reminder to practitioners to advise patients undergoing embryo transfer of the primary ovarian pregnancy risk. Information is provided herein regarding the diagnosis and management of primary ovarian pregnancy in women treated with in vitro fertilization. We review the criteria for early diagnosis and treatment options.

Adult↗

Blastocyst quality affects the success of blastocyst-stage embryo transfer.

OBJECTIVE: To determine the relationship between blastocyst quality and the results of embryo transfer at the blastocyst stage. DESIGN: Retrospective case analysis. SETTING: Tertiary care private hospital IVF center. PATIENT(S): A total of 350 blastocyst-stage embryo transfer cycles. INTERVENTION(S): In vitro culture to the blastocyst stage was undertaken in 350 ICSI cycles where four or more cleavage-stage embryos were available on day 3. MAIN OUTCOME MEASURE(S): Relationship between blastocyst quality and implantation and clinical and multiple pregnancy rates. RESULT(S): Transfer of at least one grade 1 or grade 2 blastocyst or one hatching blastocyst was associated with very high implantation and pregnancy rates. However, transfer of grade 3 blastocysts yielded very low implantation and pregnancy rates. CONCLUSION(S): There appears to be a strong correlation between blastocyst quality and success of blastocyst transfer.

Blastocyst↗

[Laparoscopic aspiration of oocytes for in vitro fertilization and embryo transfer].

Within the in vitro fertilization and embryo transfer procedure, 127 laparoscopies were performed in 89 women. The only indication was tubal infertility. There were 116 gonadotropin stimulated cycles and 11 clomiphene citrate stimulated cycles. Because of a limited ovarian access laparoscopic adhesiolysis was necessary in 30%. Egg recovery amounted to 440 oocytes in 92% successful laparoscopies, which represents 4.1 oocytes per laparoscopy. This resulted in 15 pregnancies of which 3 ended with spontaneous abortion, 6 biochemical and 6 ongoing pregnancies. Two pregnancies resulted in the live birth of normal twins, and one in the birth of a healthy girl.

Embryo Transfer↗

Equine embryo transfer.

Current procedures for collection and transfer of equine embryos are presented. Factors affecting embryo recovery and pregnancy rates after transfer are discussed, and morphologic assessment and development of the embryo are described.

Animals↗

Fertility nurses doing embryo transfers -- what is the impact of training?

It has been demonstrated that embryo transfer during IVF treatment can be performed competently and successfully by nurses (Barber et al., 1996). The present study has examined the success of nurses in training using the standardized protocol of this Unit. Initially, three nurses (two experienced (training completed) and one inexperienced (training ongoing)) each performed 80 transfers, which were standardized to three embryos replaced per transfer. The study aimed to establish whether a standardized procedure was undertaken by the nurses and to assess the influence of one inexperienced nurse performing the procedure. A further study (study 2) was performed to assess the influence of three inexperienced nurses against three experienced nurses undertaking the same procedures. In study 1, the pregnancy rates were 27.5%, 38.8% and 40.0% and there was no significant difference in the clinical pregnancy rates. In study 2, the pregnancy rates were 18.7%, 20.0% and 20.0% for the inexperienced nurses, and 26.3%, 30.0% and 32.5% for the experienced nurses. There was no significant difference in the clinical pregnancy rates within the inexperienced group or the experienced group. When the results of the three inexperienced nurses were grouped and were compared with those of the three experienced nurses, the pregnancy rates were 19.5% and 29.5%, respectively (P < 0.02). It has been shown that good clinical pregnancy rates can be achieved when nurses perform embryo transfer. There is no significant effect on clinical results when one nurse is in training; however, because of the expected learning curve, when three nurses train together a more significant effect is observed.

Journal Article↗

Cigarette smoking at time of in vitro fertilization cycle initiation has negative effect on in vitro fertilization-embryo transfer success rate.

PURPOSE: To assess cigarette smoking of female patients prior to starting in vitro fertilization cycle and possible affect on subsequent in vitro fertilization-embryo transfer outcome. METHODS: Retrospective study involving 340 consecutive patient questionnaires filled out at time of in vitro fertilization program entry. Only cycles resulting in embryo transfer after transvaginal ultrasound directed ovum retrieval (n = 253) were considered. The three patient pregnancy outcomes of not pregnant, spontaneous abortion, and live birth, were cross-referenced with smoking and nonsmoking patients. RESULTS: No significant difference found in overall pregnancy rate per embryo transfer for smokers (35%) vs nonsmokers (31%). However, the abortion rate was significantly higher for the smokers (73%) vs nonsmokers (24%) with a P value < 0.001. CONCLUSIONS: Results suggest preentry in vitro fertilization cycle cigarette smoking has adverse affect on potential pregnancy outcome by increasing spontaneous abortion. Preconception health consultation concerning adverse cigarette smoking effects should be implemented prior to program entry.

Abortion, Spontaneous↗

Ultrasound-guided embryo transfer: a meta-analysis of randomized controlled trials.

OBJECTIVE: To conduct a meta-analysis of randomized controlled studies to evaluate abdominal ultrasound-guided embryo transfer compared to the clinical touch method. DESIGN: Meta-analysis. SETTING: Four studies performed in academic research centers in Barcelona, Vizcaya, Hong Kong, and Madrid. PATIENT(S): A total of 2,051 patients: 1,024 received ultrasound-guided embryo transfers and 1,027 received clinical touch method transfers. INTERVENTION(S): Fourteen studies were retrieved from the literature, but only four of them fitted our selection criteria. The meta-analysis was conducted using the RevMan software with the Peto-modified Mantel-Haenszel method and the fixed effect model. MAIN OUTCOME MEASURE(S): The primary outcome measures were the clinical pregnancy and ongoing pregnancy rates. The secondary outcome measures were the incidences of ectopic pregnancies, miscarriage rate, multiple pregnancies, and difficult transfers. RESULT(S): Compared to the clinical touch method, abdominal ultrasound-guided transfer significantly increased the clinical pregnancy rate and the ongoing pregnancy rate. There was no effect on the incidence of ectopic pregnancy, multiple pregnancy, or miscarriage rate. CONCLSUION(S): Ultrasound-guided embryo transfer increases the clinical pregnancy and ongoing pregnancy rates significantly compared to the clinical touch method.

Abortion, Spontaneous↗

Embryo survival and conceptus growth after reciprocal embryo transfer between Chinese Meishan and Landrace x Large White gilts.

Embryos were transferred between Meishan and Landrace x Large White (control) gilts on Day 4 or 5 to establish approximately equal numbers of all four possible combinations of donor breed and recipient breed. The breed of the donor gilt significantly (P less than 0.01) affected embryo survival with 44.5% of transferred Meishan embryos and 69.6% of transferred control embryos surviving to Day 30 +/- 1. There was no influence of the breed of the recipient gilt on the proportion of embryos which survived. These differences in embryo survival between the two breeds could not be explained by differences in (1) the number of embryos transferred, (2) the stage of development of the embryos transferred, (3) the interval between ovulation and transfer or (4) the degree of asynchrony between donor and recipient gilt. On Day 30 +/- 1 embryos from control donors developed into longer fetuses (P less than 0.01) with larger allantoic sacs (P less than 0.05) than did embryos from Meishan donors. Fetuses in control recipients were longer (P less than 0.01), heavier (P less than 0.001) and had larger allantoic sacs (P less than 0.05) than fetuses occupying Meishan uteri. The interaction between breed of donor gilt and breed of recipient gilt did not significantly affect conceptus growth. These results suggest that Meishan pig embryos may be less tolerant to routine embryo transfer procedures than those of control gilts, that the genotype of the dam does not affect the proportion of embryos surviving to Day 30 +/- 1, and that both fetal and maternal factors affect conceptus growth.

Animals↗

Efficacy of a human embryo transfer medium: a prospective, randomized clinical trial study.

PURPOSE: The aim of this prospective, randomized trial was to evaluate the efficacy of Embryo-Glue as a human embryo transfer medium in IVF/ICSI cycles. METHOD: A total of 815 nonselected patients undergoing IVF/ICSI treatment between September 2003 and February 2004 were randomly allocated into the test (417 patients) and the control (398 patients) groups. In both groups, embryos were cultured in G-1ver 3, supplemented with 10% recombinant human albumin. On the day of embryo transfer (day 3), the best or good quality embryos were selected for intrauterine transfer. In the test group, the selected embryos were treated with EmbryoGlue prior to the transfer, whereas in the control group they were transferred without any treatment. RESULTS: The patients' characteristics such as age and the number of ART cycles and also the number of patients in each indication of infertility and the number of embryos selected for transfer were all similar between the two groups. In the test group, the clinical pregnancy rate in the tubal factors and the implantation rate in the tubal factors and recurrent implantation failures increased significantly compared with those in the control group. In the test group, life birth and the triplet delivery rates increased significantly compared with those in the control group. CONCLUSION: EmbryoGlue is a useful embryo transfer medium, and at least in some infertile patients it can improve clinical implantation and ongoing pregnancy rates.

Adult↗

Early pregnancy loss is significantly higher after day 3 single embryo transfer than after day 5 single blastocyst transfer in GnRH antagonist stimulated IVF cycles.

The current study aimed to investigate whether single day-3 embryo transfer (SET) results in higher early pregnancy loss (EPL) than single blastocyst transfer (SBET). A total of 896 patients underwent 1103 IVF cycles with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. In 603 cycles (D3 group) a single embryo on day 3 of the embryo culture was transferred, whereas in the remaining 500 cycles a single blastocyst was transferred on day 5 (D5 group). Multifollicular ovarian stimulation was performed with a GnRH antagonist protocol starting on day 6. SET resulted in 209 pregnancies (34.7%), compared with 221 pregnancies (44.2%) for SBET. Early pregnancy loss rate was significantly higher with SET compared with SBET (26.8% versus 17.2%, P = 0.017) and ongoing implantation rate was also significantly higher with day 5 compared with day-3 embryo transfer (OR:1.68, 95% confidence interval:1.31-2.18). Sub-optimal embryo selection for transfer on day 3, in addition to asynchronization between altered endometrium and early exposure of cleavage-stage embryos, might explain the above difference. Nevertheless, the higher implantation potential of the blastocyst questions the rationale behind performing single embryo transfer on day 3 of embryo culture in women under 36 years old.

Adult↗

Bovine nuclear transfer embryo development using cells derived from a cloned fetus.

Many different cell types have been used to generate nuclear transfer embryos and fetuses. However, little is known about the potential of fibroblasts derived from a nuclear transfer fetus as donor cells for nuclear transfer. The ability of cloned fetuses or animals to be cloned themselves is of great interest in determining whether successive generations of clones remain normal or accumulate genetic or phenotypic abnormalities. We generated a bovine fibroblast cell line from a cloned fetus, that continued to divide beyond 120 days (94 doublings,18 passages) in continuous culture. As long-term survival of cells in culture is a desirable characteristic for use in transgenic cell production, passage 2 and 18 cells were compared as donor cells for nuclear transfer (NT). When cells from passage 2 (2 weeks in culture) and passage 18 (4 months in culture) were used for nuclear transfer, there was no significant difference in development rate to blastocyst (35.4 versus 44.6%, P=0.07). A greater proportion of late passage cells were in G0/G1 whether under serum-fed (64 versus 56%, P<0.01) or serum-starved (95 versus 88%, P<0.01) culture conditions. Following embryo transfer, equivalent day 30 pregnancy rates were observed for each group (P 2: 2/19 versus P 18: 2/13). A slightly retarded fetus was surgically removed at day 56 and the remaining three fetuses died in utero by day 60 of gestation. Our results show that fibroblast cells derived from regenerated cloned fetuses are capable of both in vitro and in vivo development. The longevity of this regenerated cell line would allow more time for genetic manipulations and then to identify stable transfected cells prior to their use as NT donor cells. Although no live fetuses were produced in this study the results provide encouraging data to show that a cloned fetus can itself be recloned to produce another identical cloned fetus. Further studies on this and other recloned fetuses are necessary to determine whether the failure to produce live offspring was a result of inadequate sample size or due to the cell type selected.

Animals↗