Blastocyst development on day 5 - A relationship to clinical pregnancy rate?

Abstract

Objective: Transfer of multiple embryos to the uterus often results in a high order multiple gestation. In an effort to reduce this risk while maximizing the pregnancy rate, we culture to Day 5 (D5) the embryos of those patients who meet our criteria and transfer an optimal number based on our evaluation of embryo quality; this enables us to replace fewer embryos than was previously done on Day 3 (D3). Pregnancy and implantation rates were analyzed relative to the developmental status of the lead embryo on D5. Design: Retrospective analysis of all cycles utilizing D5 embryo transfer (ET) from 1/2000 to 3/2002 at a large university-based IVF program. We examined the cycles of patients ≤37 (n=584) and 38–42 (n=185) years old. Materials/Methods: Following retrieval, oocytes were fertilized by insemination or ICSI. Patients having ≥3 good quality embryos on D3 were eligible for D5 ET. Embryos were cultured in various media systems (G media, IVF Scandinavia; P media, Irvine Scientific; and Quinns media, Sage Biopharma). Blastocyst developmental stage and quality were graded according to Gardner. Data were analyzed by Fisher Exact or χ2 tests with p <0.05. Results: Pregnancy (PR) and implantation (IR) rates were positively correlated to the developmental status of the lead blastocyst on D5 (see Table). When only morulae or stage 1 blastocysts were transferred, the pregnancy rates were significantly lower than those for advanced stage blastocysts. Although not presented, a similar pattern was also observed in oocyte donation cycles. Furthermore, analysis of the distribution of development stages on D5 revealed that significantly more of the embryos of young patients progressed to blastocyst stage 3 or greater than in the older age group (63% versus 53%, p <0.001) suggesting a reduced developmental potential in the older patients. We routinely transfer 2 embryos to patients ≤37 years of age and 3 embryos to patients ≥38 years old. Based on the lower PR and IR when only morulae and stage 1 blastocysts were available, we often transfer an additional embryo when the lead embryo has not progressed beyond a morula or stage 1 blastocyst. To date, there have been 15 triplet(+FH) gestations out of 332 pregnancies (4%) in the young patients, a group especially at risk for high order multiples. However, 8 of these triplets were due to monozygotic twinning when only 2 embryos were transferred.TableRelationship of lead embryo stage at transfer to clinical pregnancy (PR, +FH) and implantation rates (IR, sac).StageIVF patient Age≤37 years old38–42 years oldPR (%)IR (%)PR (%)IR (%)Morula19/65 (29)30/174 (17)4/21 (19)8/77 (10)Stage 118/52 (35)28/134 (21)8/25 (32)12/91 (13)Stage 253/100 (53)95/251 (38)21/41 (51)35/137 (26)Stage 3101/160 (63)162/349 (46)24/47 (51)35/149 (23)Stage 4127/188 (67)218/388 (56)24/44 (55)47/128 (37)Stage 514/19 (74)22/38 (58)3/7 (43)5/19 (26)(ba, p < 0.05, dc, p < 0.05). Open table in a new tab (ba, p < 0.05, dc, p < 0.05). Conclusions: Because the developmental stage of the lead blastocyst on D5 can predict pregnancy outcome, it may be used to determine a number of embryos for transfer that maintains a high pregnancy rate but minimizes the potential for a high order multiple gestation. This includes limiting transfers to 2 embryos when the lead BL is stage 3 or higher and increasing the number of embryos when the lead BL is grade 1 or a morula. Patients eligible for a 3 embryo transfer on D5 should be aggressively counseled about the possibility of a triplet outcome. Supported by: None.