IMSI vs. ICSI: Does high magnification sperm selection improve outcomes?

February 25, 2013Carole 2 Comments »

Selecting the best sperm for ICSI is not a big deal if most of the sperm are normal.  Where it becomes more tricky is when you are hard pressed to find a normal appearing sperm in the sample. Some defects like sperm with two heads, huge heads, two tails, kinked tails are easy to detect and avoid with standard magnification. Other defects, like vacuoles in the sperm head are not always glaringly obvious at the lower magnification (300x) used for selecting sperm for ICSI. In 2001 Benjamin Bartoov, PhD, published his work showing that high magnification selection of normal sperm free of head vacuoles resulted in better pregnancy rates. His 2004 publication further supported his conclusion that the ability to identify sperm with normal nuclear morphology using high magnification motile sperm organellar morphology examination (MSOME) was responsible for the better outcomes associated with IMSI.

Does IMSI produce better pregnancy and high birth rates for every patient? The clinical studies directly comparing ICSI to IMSI have not been entirely consistent with some studies showing benefit and others showing no benefit of using high power (1600-2500X) morphological selection of sperm.

Intracytoplasmic morphologically selected sperm injection versus intracytoplasmic sperm injection: a step toward a clinical algorithm. Klement AH, Koren-Morag N, Itsykson P, Berkovitz A. Fertil Steril. 2013 Jan 25. doi:pii: S0015-0282(12)02529-0. 10.1016/j.fertnstert.2012.12.020. [Epub ahead of print

Summary: Study was performed in a single study at one center comparing 1,891 IVF-ICSI cycles versus 577 IVF-IMSI. In first IVF cycles, either technique was equally effective in producing pregnancies and life births so first cycles saw no difference. However, in second cycles after the first ICSI cycle failed, using IMSI to identify normal sperm showed a better pregnancy rate   (56% vs. 38% PRs and 28% vs. 18% delivery rates, respectively).

Intracytoplasmic morphologically selected sperm injection (IMSI) vs intracytoplasmic sperm injection (ICSI) in patients with repeated ICSI failure. González-Ortega C, Cancino-Villarreal P, Pérez-Torres A, Vargas-Maciel MA, Martínez-Garza SG, Pérez-Peña E, Gutiérrez-Gutiédrrez AM. Ginecol Obstet Mex. 2010 Dec;78(12):652-9. Spanish, abstract translated.

Summary: In this smaller study, the clinic compared the success rate of sperm injection cycles before and after the date in which IMSI was introduced into the clinic. Specifically, lab technicians were using an IMSI procedure called motile sperm organelle morphology examination (MSOME) at 6600X magnification, in which the absence of visible sperm head vacuoles was required for a sperm to be judged as normal and suitable for injection. IMSI was used for couples who had two or more failed ICSI cycles and their success rates were compared with the last 30 standard ICSI  cycles of patients with similar characteristics .The IMSI pregnancy rate was better than with ICSI (63 vs. 50%), but was not statistically significant for the small case number. However, the implantation rate was superior with IMSI vs. ICSI.  (44.8%vs. 29.7%).

The IMSI procedure improves poor embryo development in the same infertile couples with poor semen quality: a comparative prospective randomized study. Knez K, Zorn B, Tomazevic T, Vrtacnik-Bokal E, Virant-Klun I.Reprod Biol Endocrinol. 2011 Aug 29;9:123. doi: 10.1186/1477-7827-9-123. Free PMC Article

Summary: In this small study of 20 IMSI cycles vs 37 ICSI cycles, fertilization rate, embryo development, implantation, pregnancy and abortion rates were compared. With IMSI, the were more blastocysts per cycle than in the ICSI group at day 5 and fewer cycles with arrested embryos, suggesting that better embryo quality was achieved with use of high power morphological selection. There was a trend toward higher implantation and pregnancy rates, although the results were not statistically significant.

Pregnancy outcomes in women with repeated implantation failures after intracytoplasmic morphologically selected sperm injection (IMSI). Oliveira JB, Cavagna M, Petersen CG, Mauri AL, Massaro FC, Silva LF, Baruffi RL, Franco JG Jr. Reprod Biol Endocrinol. 2011 Jul 22;9:99. doi: 10.1186/1477-7827-9-99.Free PMC Article

Summary: In this medium sized study, 200 patients with at least two previous failed ICSI cycles were enrolled in the study, and had either ICSI or IMSI. IMSI was performed at 8400X magnification vs. ICSI at 400x magnification. Patients in both groups were similar in the following respects:  age, number failed cycles, infertility diagnosis, percentage of normal sperm found via MSOME analysis, semen analysis results, total number of mature oocytes collected, and number of high quality embryos transferred.  When the clinical outcomes for each group were compared, there was no statistically significant difference in rates of fertilization, implantation and pregnancy rate. Even rates of miscarriage, although trending toward significance,  did not reach statistical significance  (IMSI:15.3% vs ICSI:31.7%), ongoing pregnancy (IMSI:22% vs ICSI:13%) and live births (IMSI:21% vs ICSI:12%). A larger study may show significance.

[Intracytoplasmic morphologically selected sperm injection of testicular sperm: clinical outcome in azoospermia patients]. Ai L, Liu SY, Huang J, Chen SW, Liu J, Zhong Y. Zhonghua Nan Ke Xue. 2010 Sep;16(9):826-9. Chinese, abstract translated.

Summary: This small study compared 66 ICSI cycles vs 39 IMSI cycles using testicular sperm instead of ejaculated sperm. No significant differences were found in either  rates of pregnancy (51.52% vs. 56.41%) and implantation (30.67% vs. 35.29%) in the two groups. However, the miscarriage rate was lower with IMSI  (4.50% vs. 11.76%).

Morphological nuclear integrity of sperm cells is associated with preimplantation genetic aneuploidy screening cycle outcomes. Figueira Rde C, Braga DP, Setti AS, Iaconelli A Jr, Borges E Jr. Fertil Steril. 2011 Mar 1;95(3):990-3. doi: 10.1016/j.fertnstert.2010.11.018. Epub 2010 Dec 4.

Summary: Sixty cycles of IMSI were compared to 6o ICSI cycles in older patients who were undergoing IVF to create embryos for PGS aneuploidy testing. The sperm nucleus was specifically examined using IMSI. Interestingly, standard ICSI cases had a higher incidence of sex-chromosome aneuploidy (23.5% vs. 15.0%, respectively) and chaotic embryos. (27.5% vs. 18.8%).  The cycle cancellation rate-due to aneuploid embryos- was also significantly higher in ICSI cycles (11.8% vs. 2.5%).

Intracytoplasmic morphologically selected sperm injection improves development and quality of preimplantation embryos in teratozoospermia patients Knez K, Tomazevic T, Zorn B, Vrtacnik-Bokal E, Virant-Klun I. Reprod Biomed Online. 2012 Aug;25(2):168-79. doi: 10.1016/j.rbmo.2012.03.011. Epub 2012 Apr 3.

Summary: In this prospective randomized study, 52 IMSI cycles were compared to 70 standard ICSI cycles in patients with teratozoospermia. Sperm were selected via IMSI for the absence of vacuoles in the head. A statistically significantly higher pregnancy rate was observed when IMSI was used for these patients. Furthermore, patients whose eggs were fertilized with sperm lacking head vacuoles had more normal looking zygotes, more embryos went to blastocyst stage.

So the picture that emerges is that IMSI, while promising,  may not deliver better outcomes for all patients and is not necessarily indicated for all patients. But in specific subtypes of patients who have failed with standard ICSI, are of advanced maternal age or have partners with teratozoospermia, IMSI does seem to provide an advantage obtaining higher quality embryos that are better able to progress, implant and continue to a live birth.

However, even with the potential to provide better outcomes, technical proficiency at using IMSI by one technician or one lab compared to another are critical for realizing the potential advantage of IMSI. If you are being offered IMSI by your clinic, you should still ask questions about how long IMSI has been offered and what the outcomes are for patients with similar profiles to yours. IMSI requires an investment in both new equipment and retraining of technicians. There is always pressure to bring new services on-line as quickly as possible.  Every new technique has a learning curve where outcomes are not yet optimal and you don’t want to be at the steep end of the curve before results are optimized. It is important to have a good idea of the clinic’s proficiency with IMSI -just like any new technique- before you enroll in a new treatment plan so don’t be afraid to ask questions.

© 2013, Carole. All rights reserved.

2 Responses to this entry

  • curious Says:

    Dear Carole,

    Thank you for a great article. Can IUI with higher magnification selected sperms be done to reduce miscarriage rate?


  • Carole Says:

    Hi Curious,
    There is no sperm selection on a per sperm basis for IUI. Your techs can perform sperm washing procedures to generally improve the ejaculate for IUI, by removing the debris and really “out of norm” sperm, but higher magnification of each sperm is impossible for an ejaculate of 20 million sperm. If you are doing IVF with ICSI, then your tech can hand-select the best sperm for injection into an egg. Hope that helps.

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