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Does the timing of mock embryo transfer affect in vitro fertilization implantation and pregnancy rates?

2007; Elsevier BV; Volume: 88; Issue: 5 Linguagem: Inglês

10.1016/j.fertnstert.2006.12.057

1556-5653

Kathleen O. Katariya, G. Wright Bates, Randal D. Robinson, Nancy J. Arthur, Anthony M. Propst,

Reproductive Biology and Fertility

The timing of a mock embryo transfer does not affect in vitro fertilization implantation or pregnancy rates. Performing a mock embryo transfer at the time of oocyte retrieval, 3 to 5 days before embryo transfer, does not have a deleterious effect on the endometrium. The timing of a mock embryo transfer does not affect in vitro fertilization implantation or pregnancy rates. Performing a mock embryo transfer at the time of oocyte retrieval, 3 to 5 days before embryo transfer, does not have a deleterious effect on the endometrium. The goal of an embryo transfer (ET) is to deliver the embryos to the optimal location in the uterine cavity to achieve a successful pregnancy. The ET is a critical step that directly influences implantation. Over the past 10 years, additional emphasis has been placed on ET technique (1Kovacs G.T. What factors are important for successful embryo transfer after in-vitro fertilization?.Hum Reprod. 1999; 14: 590-592Crossref PubMed Scopus (105) Google Scholar). Several investigators have reported that difficult transfers and factors related to difficult transfers lead to decreased ET success rates (2Mansour R. Aboulghar M. Serour G. Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate in human in vitro fertilization.Fertil Steril. 1990; 54 (678–1)PubMed Google Scholar, 3Schoolcraft W.B. Surrey E.S. Gardner D.K. Embryo transfer: techniques and variables affecting success.Fertil Steril. 2001; 76: 863-870Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar). Despite a lack of evidence-based support, a mock (or practice) embryo transfer (MET) is commonly performed to assess variables such as uterine cavity measurement, position, ease of transfer, and the choice of appropriate transfer catheter to prepare for an atraumatic and accurate delivery of embryos at the time of actual ET (2Mansour R. Aboulghar M. Serour G. Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate in human in vitro fertilization.Fertil Steril. 1990; 54 (678–1)PubMed Google Scholar, 4Knutzen V. Stratton C.J. Sher G. McNamee P.I. Huang T.T. Soto-Albors C. Mock embryo transfer in early luteal phase, the cycle before in vitro fertilization and embryo transfer: a descriptive study.Fertil Steril. 1992; 57 (156–2)PubMed Google Scholar). With the great variability of cervical and uterine anatomy, trial transfers preceding in vitro fertilization (IVF) may decrease difficult transfers (3Schoolcraft W.B. Surrey E.S. Gardner D.K. Embryo transfer: techniques and variables affecting success.Fertil Steril. 2001; 76: 863-870Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar). Mansour et al. (2Mansour R. Aboulghar M. Serour G. Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate in human in vitro fertilization.Fertil Steril. 1990; 54 (678–1)PubMed Google Scholar), in a small unblinded study, showed that in a MET group, the implantation and pregnancy rates were 7.2% and 22.8%, respectively, compared with 4.3% and 13.1% in the non-MET group. Goudas et al. (5Goudas V.T. Hammitt D.G. Damario M.A. Session D.R. Singh A.P. Dumesic D.A. Blood on the embryo transfer catheter is associated with decreased rates of embryo implantation and clinical pregnancy with the use of in vitro fertilization-embryo transfer.Fertil Steril. 1998; 70 (878–2)Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar) suggested that emphasis on atraumatic ET technique may improve IVF success rates. In addition, it is possible that the timing of MET may also influence ET success rates. A MET performed at the time of oocyte retrieval may negatively affect the endometrial environment, thus affecting the initial interaction between embryonic cells and endometrial cells. Altered endometrial receptivity could have a direct impact on the implantation and pregnancy rates. The purpose of this study was to evaluate if there is a difference in implantation and pregnancy rates for a MET performed either before an IVF cycle or at the time of oocyte retrieval. We would expect that the implantation and pregnancy rates would be higher in an early MET, reflecting less endometrial disruption at the time of actual ET. We performed a retrospective, cohort study that included all women who underwent a cycle of IVF-ET at Wilford Hall Medical Center between January 2002 and May 2005. The study protocol was approved by our institutional review board. There were no conflicts of interest. All patients underwent MET, either at a pre-IVF office visit (before the start of ovulation induction for IVF) or at the time of oocyte retrieval. All MET and actual ET procedures were performed by one of three board-certified reproductive endocrinologists. Subsequent IVF cycles (with or without a MET) were excluded from analysis. We reviewed 289 IVF cycles in 289 women, 23 to 40 years of age. Patients who had had the MET (n = 103) before starting ovulation induction for IVF were compared with a similarly aged group of patients (n = 186) who had a MET during the oocyte retrieval, 3 to 5 days before their ET. The MET were performed using a Cook Insemi-Cath (Cook Ob/Gyn, Spencer, IN) to sound the uterus without ultrasound guidance. The uterine cavity length at MET (defined as the distance in centimeters from the external cervical os to the uterine fundus) was recorded. Stimulation protocols for IVF were individualized to the patient's medical history, ovarian reserve, and ovarian response but generally were similar between the groups, with most patients using a gonadotropin-releasing hormone (GnRH) antagonist protocol. Ganirelix acetate was started when lead follicles were 13–14-mm mean diameter on transvaginal ultrasound. Human chorionic gonadotropin (hCG), 5000–10,000 IU SC, was administered when at least two follicles were a mean diameter of ≥18 mm, with at least two additional follicles greater than 10 mm. Oocyte retrieval was performed 36 hours later, and embryos were transferred on either day 3 or 5 after retrieval, depending on embryo number and quality. Patients received luteal support with IM progesterone (50 mg daily). One to four embryos were transferred 3 to 5 days after oocyte retrieval, with a mean (± SD) of 2.2 in the early MET and 2.4 in the oocyte retrieval MET group (P=.005). All ET were performed using an 18-cm soft Wallace Embryo Replacement catheter (Smiths Medical International, Ltd, Hythe, Kent, United Kingdom) under transabdominal ultrasound guidance. The goal for the optimal depth for ET was 15 to 20 mm from the endometrial stripe fundus. The uterine transfer depth was defined as the transfer distance in centimeters measured from the external cervical os using catheter centimeter markings. The subjective ease of the ET was also recorded. All analyses were accomplished using SPSS v.13 for Windows (SPSS, Inc., Chicago, IL). Exploratory data analysis was initially performed to determine normality of the data. The parametric continuous variables were analyzed using the Student's t-test. The nonparametric continuous or ordinal data were analyzed with the Mann-Whitney U test. Percentages or rates were compared using the chi-square or Fisher's exact test, where indicated. There were no differences between the two groups with respect to age, body mass index, and use of intracytoplasmic sperm injection (Table 1). Both groups had a similar number of oocytes and embryos, although the oocyte retrieval MET group had a higher mean (± SD) number of embryos transferred compared with the early MET group (2.4 vs. 2.2, P=.005) (see Table 1). The degree of difficulty of MET between the groups was similar, with 9.7% difficult transfers in the early MET group versus 15.1% difficult transfers in the MET at oocyte retrieval group (P=.27). The early MET and oocyte retrieval MET groups had similar implantation (40.1% vs. 33.2%) and ongoing pregnancy rates (47.6% vs. 48.4%) (see Table 1). Implantation rate was defined as the number of total gestational sacs divided by the total number of embryos transferred. Clinical pregnancy was defined as the presence of a gestational sac visualized on ultrasound 4 to 6 weeks after ET.Table 1Comparison of patients who underwent early mock embryo transfer (MET) and patients who had MET during oocyte retrieval, 3 to 5 days before embryo transfer.ParameterEarly MET (n = 103)Oocyte retrieval MET (n = 186)P value or OR (95% CI)Age (years)33.233.2.936Body mass index25.825.4.670ICSI46 (44.6%)72 (38.7%).324Peak estradiol18442435.006No. of oocytes12.011.0.441No. of mature oocytes11.511.6.917No. of embryos8.18.0.822No. of embryos transferred2.22.4.005Difficult transfer9.7%15.1%.270Mean length of cavity at MET7.6 ± 0.85 cm7.9 ± 0.94 cm.003Mean depth of cavity at actual ET6.7 ± 0.91 cm6.9 ± 0.85 cm.080Positive hCG (per ET)59.2%60.8%0.94 (0.56, 1.58)Clinical pregnancy (per ET)55.3%53.2%1.09 (0.65, 1.82)Implantation rate (gestational sacs/ET)40.1% (75/187)33.2% (126/339)1.34 (0.95, 1.90)Ongoing pregnancy (per ET)47.6%48.4%0.97 (0.58, 1.61)Katariya. Mock embryo transfer. Fertil Steril 2007. Open table in a new tab Katariya. Mock embryo transfer. Fertil Steril 2007. The length of the uterine cavity at the time of MET was statistically different between the early MET and the oocyte retrieval MET groups. The mean (± SD) length of the uterine cavity in the early MET group was 7.6 ± 0.85 cm, and the cavity length in the MET at oocyte retrieval group was 7.9 ± 0.94 cm (P=.003). This suggests that that the uterus changes size during the IVF-ET stimulation regimens. The change in uterine cavity length during IVF may be in part due to change in ovarian size during controlled ovarian hyperstimulation. Henne and Milki (6Henne M.B. Milki A.A. Uterine position at real embryo transfer compared with mock embryo transfer.Hum Reprod. 2004; 19: 570-572Crossref PubMed Scopus (35) Google Scholar) reported that 55% of patients with a retroverted uterine position at MET changed to an anteverted position at ET. It is interesting that 33% of retroverted uteri changed to anteverted for frozen-thawed ET, suggesting that factors other than increased ovarian volume may play a role in uterine position change (6Henne M.B. Milki A.A. Uterine position at real embryo transfer compared with mock embryo transfer.Hum Reprod. 2004; 19: 570-572Crossref PubMed Scopus (35) Google Scholar). Furthermore, ultrasound analysis of the uterine cavity length at ET has shown that it varies from the cavity length determined by a MET in prior studies, which may suggest a difference in precycle uterine cavity depth measurement (7Anderson R.E. Nugent N.L. Gregg A.T. Nunn S.L. Behr B.R. Transvaginal ultrasound-guided embryo transfer improves outcome in patients with previous failed in vitro fertilization cycles.Fertil Steril. 2002; 77 (769–5)Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 8Gergely R.Z. DeUgarte C.M. Danzer H. Surrey M. Hill D. DeCherney A.H. Three dimensional/four dimensional ultrasound-guided embryo transfer using the maximal implantation potential point.Fertil Steril. 2005; 84: 500-503Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 9Woolcott R. Stanger J. Potentially important variables identified by transvaginal ultrasound-guided embryo transfer.Hum Reprod. 1997; 12: 963-966Crossref PubMed Scopus (123) Google Scholar, 10Pope C.S. Cook E.K.D. Arny M. Novak A. Grow D.R. Influence of embryo transfer depth on in vitro fertilization and embryo transfer outcomes.Fertil Steril. 2004; 81: 51-58Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar). This poses the question of the utility of obtaining the uterine cavity length at MET by sounding (10Pope C.S. Cook E.K.D. Arny M. Novak A. Grow D.R. Influence of embryo transfer depth on in vitro fertilization and embryo transfer outcomes.Fertil Steril. 2004; 81: 51-58Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar). Appropriate direction of the catheter following the contour and length of the endometrial cavity is critical to avoid subtle disruption of the endometrium, which may affect implantation, and to prevent eliciting harmful myometrial contractions, which may expel an embryo (3Schoolcraft W.B. Surrey E.S. Gardner D.K. Embryo transfer: techniques and variables affecting success.Fertil Steril. 2001; 76: 863-870Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar). Because ET is a critical step that directly influences implantation, it is important to investigate the biophysical variables associated with the ET technique. Studies have assessed indirect measures of trauma to the endometrium such as blood or mucus on the transfer catheter (implicated in difficult transfers), which may result in lower implantation and pregnancy rates (5Goudas V.T. Hammitt D.G. Damario M.A. Session D.R. Singh A.P. Dumesic D.A. Blood on the embryo transfer catheter is associated with decreased rates of embryo implantation and clinical pregnancy with the use of in vitro fertilization-embryo transfer.Fertil Steril. 1998; 70 (878–2)Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 11Alvero R. Hearns-Stokes R.M. Catherino W.H. Leondires M.P. Segars J.H. The presence of blood in the transfer catheter negatively influences outcome at embryo transfer.Hum Reprod. 2003; 18 (1848–2)Crossref PubMed Scopus (64) Google Scholar, 12Nabi A. Awonuga A. Birch H. Barlow S. Stewart B. Multiple attempts at embryo transfer: does this affect in-vitro fertilization outcome?.Hum Reprod. 1997; 12: 1188-1190Crossref PubMed Scopus (84) Google Scholar, 13Awonuga A. Nabi A. Govindbhai J. Birch H. Stewart B. Contamination of embryo transfer catheter and treatment outcome in in-vitro fertilization.J Assist Reprod Genet. 1998; 15 (198–1)Crossref PubMed Scopus (27) Google Scholar). Other studies have shown a greater frequency of uterine contractility after difficult ET (14Lesny P. Killick S.R. Tetlow R. Embryo transfer-can we learn anything from the observation of junctional zone contractions?.Hum Reprod. 1998; 13: 1540-1546Crossref PubMed Scopus (164) Google Scholar, 15Lesny P. Killick S.R. Tetlow R. Robinson J. Uterine junctional zone contractions during IVF and embryo transfer cycle.Hum Reprod. 1997; 12: 10-11Crossref Google Scholar, 16Franchin R. Righini C. Olivennes F. Taylor S. de Ziegler D. Frydman R. Uterine contractions at time of embryo transfer alter pregnancy rates after in vitro fertilization.Hum Reprod. 1998; 13 (1968–4)Google Scholar). Myometrial contractility, as well as secreted products of the endometrium regulated directly by ovarian steroids and indirectly by various growth factors and cytokines, can influence endometrial receptivity and the expulsion of embryos (14Lesny P. Killick S.R. Tetlow R. Embryo transfer-can we learn anything from the observation of junctional zone contractions?.Hum Reprod. 1998; 13: 1540-1546Crossref PubMed Scopus (164) Google Scholar, 15Lesny P. Killick S.R. Tetlow R. Robinson J. Uterine junctional zone contractions during IVF and embryo transfer cycle.Hum Reprod. 1997; 12: 10-11Crossref Google Scholar, 16Franchin R. Righini C. Olivennes F. Taylor S. de Ziegler D. Frydman R. Uterine contractions at time of embryo transfer alter pregnancy rates after in vitro fertilization.Hum Reprod. 1998; 13 (1968–4)Google Scholar, 17Lessey B.A. The role of the endometrium during embryo implantation.Hum Reprod. 2000; 15: 39-50Crossref PubMed Scopus (22) Google Scholar). Furthermore, many studies suggest that ET performed under ultrasound guidance is associated with increased pregnancy rates (7Anderson R.E. Nugent N.L. Gregg A.T. Nunn S.L. Behr B.R. Transvaginal ultrasound-guided embryo transfer improves outcome in patients with previous failed in vitro fertilization cycles.Fertil Steril. 2002; 77 (769–5)Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 8Gergely R.Z. DeUgarte C.M. Danzer H. Surrey M. Hill D. DeCherney A.H. Three dimensional/four dimensional ultrasound-guided embryo transfer using the maximal implantation potential point.Fertil Steril. 2005; 84: 500-503Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 9Woolcott R. Stanger J. Potentially important variables identified by transvaginal ultrasound-guided embryo transfer.Hum Reprod. 1997; 12: 963-966Crossref PubMed Scopus (123) Google Scholar, 18Matorras R. Urquijo E. Mendoza R. Corcostegui B. Exposito A. Rodriguez-Escudero F.J. Ultrasound-guided embryo transfer improves pregnancy rates and increases the frequency of easy transfers.Hum Reprod. 2002; 17: 1762-1766Crossref PubMed Scopus (104) Google Scholar, 19Sallam H.N. Sadek S.S. Ultrasound-guided embryo transfer: a meta-analysis of randomized controlled trials.Fertil Steril. 2003; 80: 1042-1046Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar). Ultrasound guidance during an ET is increasingly used to assess ET depth and to avoid touching the uterine fundus (7Anderson R.E. Nugent N.L. Gregg A.T. Nunn S.L. Behr B.R. Transvaginal ultrasound-guided embryo transfer improves outcome in patients with previous failed in vitro fertilization cycles.Fertil Steril. 2002; 77 (769–5)Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 8Gergely R.Z. DeUgarte C.M. Danzer H. Surrey M. Hill D. DeCherney A.H. Three dimensional/four dimensional ultrasound-guided embryo transfer using the maximal implantation potential point.Fertil Steril. 2005; 84: 500-503Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 9Woolcott R. Stanger J. Potentially important variables identified by transvaginal ultrasound-guided embryo transfer.Hum Reprod. 1997; 12: 963-966Crossref PubMed Scopus (123) Google Scholar). It facilitates placement of soft catheters, confirms that the catheter is beyond the internal os, and allows appropriate direction of the catheter along the endometrial cavity contour (3Schoolcraft W.B. Surrey E.S. Gardner D.K. Embryo transfer: techniques and variables affecting success.Fertil Steril. 2001; 76: 863-870Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar). Although other studies have not conclusively shown a benefit from the use of ultrasound at ET (20Flisser E. Grifo J.A. Krey L.C. Noyes N. Transabdominal ultrasound-assisted embryo transfer and pregnancy outcome.Fertil Steril. 2006; 85: 353-357Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 21Garcia-Velasco J.A. Isaza V. Martinez-Salazar J. Landazabal A. Requena A. Remohi J. Pellicer A. Simon C. Transabdominal ultrasound-guided embryo transfer does not increase pregnancy rates in oocyte recipients.Fertil Steril. 2002; 78: 534-539Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 22Kan A.K.S. Abdalla H.I. Gafar A.H. Nappi L. Ogunyemi B.O. Thomas A. Ola-ojo O.O. Embryo transfer: ultrasound-guided versus clinical touch.Hum Reprod. 1999; 14 (1259–1)Crossref PubMed Scopus (77) Google Scholar, 23Tang O.S. Ng E.H.Y. So W.W.K. Ho P.C. Ultrasound-guided embryo transfer: a prospective randomized controlled trial.Hum Reprod. 2001; 16: 2310-2315Crossref PubMed Scopus (65) Google Scholar), our experience has been that use of the transabdominal ultrasound is beneficial for improving the ease and precision of transfers. In summary, our study demonstrated that the timing of MET does not affect IVF implantation or pregnancy rates. Performing a MET at the time of oocyte retrieval, 3 to 5 days before ET, does not have a deleterious effect on the endometrium. In addition, there was a statistically significant difference in the uterine cavity length at the time of early MET when compared with MET performed at oocyte retrieval. This suggests that the uterus is dynamic; measurement of the uterine cavity length may be longer when measured closer to the time of actual ET. It is possible that assessment of the uterine cavity length closer to the time of the actual ET may be more accurate and identify yet another potential variable associated with ET success.