Trends in the Use and Indications for Intracytoplasmic Sperm Injection Between 2005 and 2017: A State-Wide Descriptive Cohort Analysis.

D. T. Carrell, A. Nyboe Andersen and D. J. Lamb Departments of Surgery (Urology), Obstetrics and Gynecology, and Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA, The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, and The Center for Reproductive Medicine, Scott Department of Urology and the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

Since its introduction in 1992, intracytoplasmic sperm injection (ICSI) has been increasingly used in patients without severe male factor infertility despite the lack of clear evidence of a benefit over conventional in vitro fertilization (IVF). Compared with pregnancies resulting from conventional IVF, pregnancies resulting from the use of ICSI are associated with 1.5 to 4 times increased risk of chromosomal abnormalities, birth defects, intellectual disabilities, imprinting disorders, and autism. Intracytoplasmic sperm injection is considerably more expensive than conventional IVF. The aim of this retrospective observational study was to assess national trends and reproductive outcomes of fresh IVF cycles associated with the use of ICSI compared with conventional IVF with respect to clinical indications for ICSI use. Although only fresh embryos were transferred, it is unlikely that outcomes for frozen-thawed embryos would differ. Data were obtained from the US National Assisted Reproductive Technology Surveillance System for all fresh and ICSI cycles performed during 1996 to 2012. The primary study outcomes were (1) trends in use of ICSI during 1996 to 2012 with respect to male factor infertility, unexplained infertility, maternal age 38 years or older, low oocyte yield (<5 oocytes retrieved), and 2 or more prior assisted reproductive technology cycles and no prior live birth, and (2) reproductive outcomes during 2008 to 2012 for conventional IVF and ICSI cycles, stratified by the presence or absence of male factor infertility. A total of 1,395,634 fresh IVF cycles were identified between1996 and 2012; 908,767 (65.1%) used ICSI, and 486,867 cycles (34.9%) used conventional IVF. Male factor infertility was identified in 499,135 (35.8%) of fresh cycles. During 2006 to 2012, ICSI use among cycles with male factor infertility increased from 76.3% (10,876/14,259) to 93.3% (32,191/34,506) (P < 0.001), whereas its use for those without male factor infertility increased from 15.4% (4,197/27,191) to 66.9% (42,321/63,250) (P < 0.001). During 2008 to 2012, 494,907 fresh IVF cycles were identified, 74.6% of which used ICSI. Male factor infertility was reported in 35.7% (176,911/494,907) of fresh cycles. The risk for multiple births among these cycles was significantly lower in those undergoing ICSI compared with conventional IVF (30.9% vs 34.2%); the adjusted relative risk (RR) was 0.87, with a 95% confidence interval (CI) of 0.83 to 0.91. Compared with conventional IVF, ICSI use among cycles without male factor infertility (n = 317,996) was associated with lower rates of implantation (23.0% vs 25.2%; adjusted RR, 0.93; 95% CI, 0.91–0.95), live birth (36.5% vs 39.2%; adjusted RR, 0.95; 95% CI, 0.93–0.97), and multiple live births (30.1% vs 31.0%; adjusted RR, 0.93; 95% CI, 0.91–0.95). These findings show that ICSI use among fresh IVF cycles in the United States increased from 36.4% to 76.2% between 1996 and 2012. The largest relative increase occurred in cycles without male factor infertility. The data show no improvement in postfertilization reproductive outcomes with use of ICSI over conventional IVF in the absence of male factor infertility, irrespective of male factor infertility diagnosis.

Intracytoplasmic sperm injection (ICSI) is increasingly used in patients without severe male factor infertility without clear evidence of a benefit over conventional in vitro fertilization (IVF). To assess national trends and reproductive outcomes for fresh IVF cycles (embryos transferred without being frozen) following the use of ICSI compared with conventional IVF with respect to clinical indications for ICSI use. Retrospective cohort study using data on fresh IVF and ICSI cycles reported to the US National Assisted Reproductive Technology Surveillance System during 1996-2012. Trends in ICSI use during 1996-2012 with respect to male factor infertility, unexplained infertility, maternal age 38 years or older, low oocyte yield, and 2 or more prior assisted reproductive technology cycles; reproductive outcomes for conventional IVF and ICSI cycles during 2008-2012, stratified by the presence or absence of male factor infertility. Of the 1,395,634 fresh IVF cycles from 1996 through 2012, 908,767 (65.1%) used ICSI and 499,135 (35.8%) reported male factor infertility. Among cycles with male factor infertility, ICSI use increased from 76.3% (10,876/14,259) to 93.3% (32,191/34,506) (P < .001) during 1996-2012; for those without male factor infertility, ICSI use increased from 15.4% (4197/27,191) to 66.9% (42,321/63,250) (P < .001). During 2008-2012, male factor infertility was reported for 35.7% (176,911/494,907) of fresh cycles. Among those cycles, ICSI use was associated with a lower multiple birth rate compared with conventional IVF (30.9% vs 34.2%; adjusted relative risk [RR], 0.87; 95% CI, 0.83-0.91). Among cycles without male factor infertility (n = 317,996), ICSI use was associated with lower rates of implantation (23.0% vs 25.2%; adjusted RR, 0.93; 95% CI, 0.91-0.95), live birth (36.5% vs 39.2%; adjusted RR, 0.95; 95% CI, 0.93-0.97), and multiple live birth (30.1% vs 31.0%; adjusted RR, 0.93; 95% CI, 0.91-0.95) vs conventional IVF. Among fresh IVF cycles in the United States, ICSI use increased from 36.4% in 1996 to 76.2% in 2012, with the largest relative increase among cycles without male factor infertility. Compared with conventional IVF, ICSI use was not associated with improved postfertilization reproductive outcomes, irrespective of male factor infertility diagnosis.

Objective The aim of this study was to compare intra-Cytoplasmic Sperm Injection (ICSI) outcomes (fertilization rate, embryo quality, pregnancy rate, and live birth rate) for couples with unexplained infertility and couples with male factor infertility, and if the quality of semen is related to ICSI outcomes. Methods This is a retrospective chart review of 2038 ICSI cycles performed between 2008 and 2014 to compare ICSI outcomes in couples with unexplained infertility and those with male factor infertility. Infertile couples were divided into 6 groups: unexplained infertility (407 patients), mild male factor infertility (not severe) either in isolation (651 patients) or combined (66 patients) with female factor infertility, severe male factor infertility either in isolation (706 patients) or combined (41 patients) with female factor infertility, female infertility in isolation (167 patients). Results Although, fertilization rates were higher in the unexplained infertility group than in the severe and mild male infertility groups (P Conclusions This study demonstrates that the use of ICSI for unexplained infertility achieved similar reproductive outcomes as male infertility cases, which are usually referred to ICSI. It also shows that the quality of semen did not positively affect ICSI outcomes.

Intracytoplasmic sperm injection does not improve the outcome of IVF treatments in patients with advanced maternal age or low oocyte number: A randomized controlled trial.

Treatment of mild/moderate male factor infertility with in vitro fertilization (IVF) instead of intracytoplasmic sperm injection (ICSI): a ten-year retrospective analysis

Obstetric and perinatal outcomes of intracytoplasmic sperm injection versus conventional in vitro fertilization in couples with nonsevere male infertility

Background: Rescue Intra Cytoplasmic Sperm Injection (ICSI) is an emergency micromanipulation endeavour aimed at salvaging the IVF ET cycle. It is aimed to save the situation in which the ART team and the couple has invested so much. Aim: The aim of this study was to assess the option of recue ICSI in cases of Fertilisation Failure (FF) in order to salvage the IVF ET. Material and Methods: This retrospective study was done in a tertiary care Assisted reproductive techniques centre of Armed Forces. Records were assessed to study the cases of fertilization failure. All those cases which had an obvious etiology for probable FF were excluded. Remaining cases where rescue ICSI was done were studied to assess its role. Study design: Retrospective Observational study Study location: A tertiary care ART centre in Armed Forces Hospitals Study duration: Dec 2018 to Dec 2020 Subjects and selection method: All couples going IVF ET for various etiologies were studied for fertilization failure. Only cases with unexplained FF were studied to assess the role of rescue ICSI. Inclusion criteria 1. Normal BMI (in the range of 18.5 to 24.5 kg/m2) 2. Normal ovarian reserves (AMH above 1.0 ng/ml) 3. Conventional IVF used for fertilization Exclusion criteria 1. Male factor infertility 2. Prior fertilisation failures 3. Advanced maternal/paternal age (Below 40 yrs) Procedure methodology: Records of all patients meeting the inclusion and exclusion criteria were studied Stimulation protocol: Antagonist protocol was used universally for stimulation in our centre. Patients were started on Inj Recombinant Follitropin Alpha (Merck Pharmaceuticals) 1050 IU/1.75 ml powder with solvent for stimulation. Personalised Stimulation protocol was started based on Age, BMI, Ovarian volume, AMH and previous stimulation data if any. Inj Ovurelix containing Citrorelix 0.25 mg from Sun Pharmaceuticals was started as antagonist on evidence of sufficient endogenous Estrogen production. Namely ultrasounds follow up showing follicular size reaching 12mm or endometrial thickness more than 6mm. On adequate stimulation with a cohort of at least 4 follicles of size 18mm, trigger was given with inj Ovitrelle 250 mcg (Contains Recombinant Choriogonadotropin Alpha,250 mcg, Merck Ltd)) and ovum pickup was done after 36-40h. Conventional Insemination was done only if post wash specimen shows a sperm concentration of more than 20 million/ml with more than 50% grade 4 motility. After denudation metaphase 2 mature oocyte without two Pronuclei stage were reassessed after 2h to rule out delayed fertilization. Those m2 oocytes which failed to fertilize were provided rescue. ICSI was done using micromanipulation disposable Injecting and holding needles from Vitromed, with bend angle of 30 degree. The holding needle had an inner diameter of 20 micro meters and injecting needle had an inner diameter of 5 micrometer. The freshly prepared semen sample was taken in PVP media under oil overlay and ICSI performed in the standard way. Results: The incidence of fertilization failure in our clientele was about 11%. Out of 415 cases, 45 patients had complete fertilization failure. Patients meeting our inclusion and exclusion criteria for FF were 23 cases. Most common cause of FF was unexplained infertility with mean duration of marriage as 9y 7mo.Overall 15% cases were due to poor ovarian reserve and with poor yield on OPU. Male factor infertility in spite of ICSI failed to fertilize in 6 cases. We obtained a fertilization rate of 41% with rescue ICSI and on further growth 56% reached 4 cell stages. Off these 21 had minimal fragmentation. Those embryos which had minimal fragmentation and equal blastomere were allowed to grow and 6 of 73 fertilized oocyte reached 8 cell stage. Conclusion The emergency rescue ICSI, in window of 18-20 hours can help salvage a cycle faced with complete fertilisation failure. It will reduce the physical and financial burden of IVF ET cycle to some extent. We conclude it is a viable option in a perplexing situation of complete fertilisation failure

To reevaluate whether relatively few oocytes obtained in one cycle are an indication for intracytoplasmic sperm injection (ICSI). A total of 406 cycles with three or fewer retrieved oocytes performed in 396 non-male infertile couples were retrospectively reviewed. Cycles were classified into three groups by different fertilization techniques: the in vitro fertilization (IVF) group, insemination with conventional IVF; the ICSI group, insemination with ICSI though semen parameters were normal; and the rescue ICSI group, re-insemination with ICSI after conventional IVF failure. The ICSI group resulted in higher normal fertilization compared with the conventional IVF group. Correspondingly, the cycle cancellation rate was decreased in the ICSI group, though it was not statistically significant. The clinical pregnancy rate and implantation rate were lower in the ICSI group compared with the conventional IVF group. Rescue ICSI was a method to avert total fertilization failure in conventional IVF, increasing fertilization and ensuring embryo availability for transfer, but the normal fertilization was the lowest due to delayed insemination and the chance of pregnancy was very little. Obtaining only few oocytes in one cycle is not considered as an indication for ICSI when the sperm sample is apparently normal. Rescue ICSI is either not recommended if conventional insemination fails. Such patients should not be subjected to the unnecessary costs and potential risks of ICSI.

Intracytoplasmic sperm injection versus conventional in vitro fertilization in unexplained infertility

Despite questionable evidence of benefits over conventional in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) use has markedly increased in recent decades among couples without male factor infertility. We assessed the frequency of ICSI use and its effect on birth outcomes. A retrospective cohort study was conducted in 141 030 women conceiving through IVF using 2006-2010 data from the Society for Assisted Reproductive Technology (SART). Between 2006 and 2010, overall ICSI use in women conceiving through IVF increased from 68.9% to 73.1%. This increase was greater among women without male factor infertility (53.0-59.2%) than in women with male factor infertility (92.0-93.4%). Women conceiving through IVF with and without ICSI had similar rates of multiple pregnancy, preterm delivery, stillbirth, and neonatal death. However, ICSI pregnancies were associated with an increased risk of birth defects over conventional IVF (3.0% for ICSI vs. 2.5% for conventional IVF; adjusted odds ratio (OR) 1.2, 95% confidence interval (CI) 1.2, 1.3). These increases were observed in both women conceiving through ICSI with male factor infertility (3.2% vs. 2.5%; OR 1.4, 95% CI 1.3, 1.5) and without male factor infertility (2.7% vs. 2.5%; OR 1.1, 95% CI 1.1, 1.2). Higher rates of birth defects were observed among women conceiving through ICSI. Since approximately half of all ICSI procedures are performed in couples without male factor infertility, ICSI may be overused in practice.

Outcome of first IVF/ICSI-cycle in couples who failed conceiving during intrauterine insemination

Results of first in vitro fertilization cycle in women with colorectal endometriosis compared with those with tubal or male factor infertility

Use and outcomes of intracytoplasmic sperm injection for non–male factor infertility

Comparison of intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (IVF in patients with non-male factor infertility.