Indication For Intracytoplasmic Sperm Injection Research Articles

Reproductive Outcomes of Conventional In Vitro Fertilization and Intracytoplasmic Sperm Injection in Patients with Non-Severe Male Infertility Across Poor and Different Sub-Optimal Ovarian Response Categories: A Cohort Study Based on 30,352 Fresh Cycles from 2009–2019

Due to the influence of economic, social and many other factors, there are more and more reproductive problems. Originally introduced for managing male factor infertility, intracytoplasmic sperm injection had become the most commonly used fertilization treatment in the world, with broadened indications including low oocyte yield, prior fertilization failure with conventional in vitro fertilization etc. However, academic evidence for better live-birth outcomes of intracytoplasmic sperm injection over conventional in vitro fertilization is limited. Thus, we aimed to compare the reproductive outcomes of conventional in vitro fertilization and intracytoplasmic sperm injection in patients with non-severe male factor infertility across poor and different sub-optimal ovarian response categories. The fertility rate, implantation rate, clinical pregnancy rate, live birth rate and other obstetric outcomes were mainly compared. Our results showed that independent of the number of oocytes retrieved, intracytoplasmic sperm injection significantly increased the fertilization rate, while conventional in vitro fertilization cycles showed a higher implantation rate, clinical pregnancy rate, and live birth rate. No differences were observed in most obstetric outcomes. Our study indicates that poor ovarian response is not an indication for intracytoplasmic sperm injection in couples with non-severe male infertility.

#244 : Reproductive Outcomes of Conventional In Vitro Fertilization and Intracytoplasmic Sperm Injection in Patients with Non-Severe Male Infertility Across Poor and Different Suboptimal Ovarian Response Categories

Background and Aims: For non-severe male factor infertility patients with poor and sub-optimal ovarian response, are there any differences in reproduction outcomes between IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) methods? Methods: Retrospective cohort study. Patients with non-severe male infertility and poor ovarian response who underwent in vitro fertilization or intracytoplasmic sperm injection at the Center for Reproductive Medicine, Peking University Third Hospital between 2009 and 2019 were included in this study (n = 30,352). Results: In all groups, intracytoplasmic sperm injection cycles involved older patients and a longer duration of infertility, while body mass index, AMH, and bFSH levels were similar. Independent of the number of oocytes retrieved, intracytoplasmic sperm injection significantly increased the fertilization rate, while in vitro fertilization cycles showed a higher implantation rate, clinical pregnancy rate, and live birth rate. No differences were observed in most obstetric outcomes, including abortion, early abortion, multiple fetus, cesarean delivery, gestational age, and congenital malformations rates. However, in vitro fertilization cycles showed higher preterm delivery rates and lower birth weights in groups with 4-6, and 7-9 oocytes retrieved. A higher female/male infant ratio was observed in intracytoplasmic sperm injection cycles when 4-6 oocytes were retrieved. Conclusions: In patients with non-severe male infertility and poor or suboptimal ovarian response, even if intracytoplasmic sperm injection increased the fertilization rate, in vitro fertilization exhibited significant advantages in implantation, clinical pregnancy, and live birth rates. Our study indicates that poor ovarian response is not an indication for intracytoplasmic sperm injection in couples with non-severe male infertility.

UTILIZATION OF INTRACYTOPLASMIC SPERM INJECTION VERSUS CONVENTIONAL IVF IN NON-MALE INFERTILITY PATIENT POPULATION: AGE BASED ANALYSIS

The primary indication for intracytoplasmic sperm injection (ICSI) is for treatment of couples with male factor infertility. However, ICSI has been proposed as a tool to overcome difficulties in sperm-oocyte interaction secondary to oocyte age and not necessarily sperm abnormalities. Our hypothesis is that ICSI might be helpful in assisting sperm penetration in oocytes from older women. Therefore, the objective of this study was to investigate if there is any advantage of performing ICSI over conventional insemination in different age groups.

Intra-Technician Comparison of Sperm Morphology Evaluation

Objective To identify intra-technician subjective variability in sperm morphology assessment at a single site. Design Intra-technician evaluation of sperm morphology results compared to reported outcome on initial semen analysis using Kruger (Tygerburg) Strict criteria. Materials and Methods This study was a retrospective analysis of 35 semen sample slides stained using a Romanowski stain (Diff-Quick). Slides were randomly selected for semen samples analyzed January 1, 2018 – February 28, 2018 and numbered (1-35). Morphology assessment was performed by 3 andrologists, blinded to initial reported morphology results. The median percentage of normal forms (normal, ≥ 4%) were compared between 3 technicians to the initial reported values. Statistical analysis was performed using One-Way Analysis of Variance (ANOVA) and ANOVA on Ranks using Kruskan-Wallis test, with p < 0.05 considered significant. Results Median percentage of normal forms was 4% for the initial semen analysis report. Whereas, technician 1: 3%, technician 2: 2% and technician 3: 3%. The median values among the technicians were significant (P = 0.021). There were no differences between reported values compared to each technician. However, the median results for technician 3 and technician 2 were different (P < 0.05). Conclusions The findings suggest that there is variability in assessment of sperm morphology between technicians. Inaccurate assessment reporting high percentage of abnormal forms for sperm morphology can result in misrepresented sperm data by clinicians. As a result, since low morphology is an indication for intra-cytoplasmic sperm injection (ICSI) during in-vitro fertilization (IVF) procedures, ICSI can be unnecessarily ordered. The additional financial cost associated with an ICSI procedure may result in financial and emotional burden for the patient. Furthermore, an incorrect abnormal morphology result leads to emotional strain on the male patient leading to the feelings of inadequacy. An increased frequency of quality assurance training of andrology technicians in groups reviewing Kruger (Tygerburg) Strict Criteria is recommended to limit assessment variability. Randomly selected images of sperm morphology from the Kruger Strict Atlas can be used to assess technician sperm morphology evaluations. Disclosures Nothing to disclose. Funding None. To identify intra-technician subjective variability in sperm morphology assessment at a single site. Intra-technician evaluation of sperm morphology results compared to reported outcome on initial semen analysis using Kruger (Tygerburg) Strict criteria. This study was a retrospective analysis of 35 semen sample slides stained using a Romanowski stain (Diff-Quick). Slides were randomly selected for semen samples analyzed January 1, 2018 – February 28, 2018 and numbered (1-35). Morphology assessment was performed by 3 andrologists, blinded to initial reported morphology results. The median percentage of normal forms (normal, ≥ 4%) were compared between 3 technicians to the initial reported values. Statistical analysis was performed using One-Way Analysis of Variance (ANOVA) and ANOVA on Ranks using Kruskan-Wallis test, with p < 0.05 considered significant. Median percentage of normal forms was 4% for the initial semen analysis report. Whereas, technician 1: 3%, technician 2: 2% and technician 3: 3%. The median values among the technicians were significant (P = 0.021). There were no differences between reported values compared to each technician. However, the median results for technician 3 and technician 2 were different (P < 0.05). The findings suggest that there is variability in assessment of sperm morphology between technicians. Inaccurate assessment reporting high percentage of abnormal forms for sperm morphology can result in misrepresented sperm data by clinicians. As a result, since low morphology is an indication for intra-cytoplasmic sperm injection (ICSI) during in-vitro fertilization (IVF) procedures, ICSI can be unnecessarily ordered. The additional financial cost associated with an ICSI procedure may result in financial and emotional burden for the patient. Furthermore, an incorrect abnormal morphology result leads to emotional strain on the male patient leading to the feelings of inadequacy. An increased frequency of quality assurance training of andrology technicians in groups reviewing Kruger (Tygerburg) Strict Criteria is recommended to limit assessment variability. Randomly selected images of sperm morphology from the Kruger Strict Atlas can be used to assess technician sperm morphology evaluations.

Should endometriosis be an indication for intracytoplasmic sperm injection (ICSI) in fresh IVF cycles?

Mechanism of infertility in endometriosis potentially involves oocyte/embryo defects and lower fertilization and implantation rates. Cumulus complex in endometriosis patients demonstrates mitochondrial dysfunction and higher oxidative stress. We sought to investigate if ICSI, which diminishes oxidative stress when compared to insemination, improves IVF outcomes in patients with endometriosis.

Should few retrieved oocytes be as an indication for intracytoplasmic sperm injection?

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.

Influence of the ovarian hyperstimulation syndrome (OHSS) in embryo quality and in implantation and pregnancy rates

OBJECTIVE: Some studies suggest that ovarian hyperstimulation can compromise implantation rates in assisted fertilization treatment cycles. Other studies believe that OHSS does not affect implantation rates or the quality of both oocytes and embryo. The purpose of this study was to evaluate embryonic quality, the implantation and pregnancy rates of patients with OHSS by comparing them to a control group without OHSS. DESIGN: Retrospective. MATERIALS AND METHODS: The study included 1905 patients with an indication for Intracytoplasmic sperm injection (ICSI) of which 156 patients had OHSS and 1749 did not (control group). Both the short and the long protocols were used. HCG was administered when at least 3 follicles had reached 19 mm in diameter. M2 eggs were injected 4 hours after oocyte retrieval. Fertilization and embryo development were assessed at 20h, 44h and 68h after ICSI. Embryo transfer was performed on day 2 or 3. Patients were divided into six groups, namely G1 (patients ≤ 35 years and with mild OHSS), G2 (patients ≤ 35 years and moderate or severe OHSS), G3 (patients between 36 to 40 years and mild OHSS), G4 (patients between 36 and 40 years and moderate to severe OHSS), G5 (patients ≤ 35 years without OHSS) and G6 (patients between 36 and 40 without OHSS). Statistical analyses used one-Way ANOVA or the Fisher's exact tests at the level of P<0.05. RESULTS: With respect to embryo quality, there was no statistically significance between the total of obtained embryos and the transferred embryos. The percentage of good morphology embryos (A+B) were: 75%, 82%, 73%, 88%, 78% and 78% for G1, G2, G3, G4, G5 and G6 respectively, and transferred embryos were: 95.5%, 100%, 98.5%, 100%, 98% and 97% for G1, G2, G3, G4, G5 and G6, respectively. Implantation rates were: 23% (G1), 56% (G2), 25% (G3), 45% (G4), 21% (G5) and 13.5% (G6). Hence, it was verified an increased implantation rate in G2 and G4 i.e., patients with a moderate or severe OHSS, as well as in the pregnancy rates, which were: 52% (G1), 72% (G2), 44% (G3), 71% (G4), 46% (G5), 47% (G6). CONCLUSIONS: Since no difference between the various groups was identified, our results do corroborate the opinion of certain authors who believe that embryo quality is not affected by OHSS. However, an increase in implantation and pregnancy rates was observed in both groups with moderate to severe OHSS i.e., G2 and G4 (≤ 35 years and 36-40 years, respectively).

Isolated teratozoospermia does not affect in vitro fertilization outcome and is not an indication for intracytoplasmic sperm injection

To reevaluate clinical management of isolated teratozoospermia, in couples initiating IVF. Retrospective analysis of fertility indices in 535 cycles. A large, university-based fertility center. Consecutive couples (n = 495) who had a semen analysis using Kruger/Tyberberg strict criteria at our center within 12 months before undergoing their first and/or second IVF cycle in 2002-2004 with >2 million postwash, motile sperm on the day of egg retrieval. Eggs were fertilized either by conventional IVF or ICSI. Semen analysis and gamete/embryo manipulation was standardized in all cases. Fertilization, fertilization failure, pregnancy, and live birth rates. There was no statistical difference in fertilization, fertilization failure, pregnancy, and live birth rates in the first or second IVF cycle when comparing couples with isolated teratozoospermia (<5% normal morphology) to those with a normal semen analysis. Furthermore, no improvement in these outcomes was noted when ICSI was used to treat these teratozoospermic couples. Because isolated teratozoospermia generally does not impact on the major indices of IVF, these patients need not be subjected to the unnecessary cost and potential risks of ICSI. Future studies, however, should focus on different sperm morphologic and biochemical parameters to determine if they are important for clinical management in IVF.

P-614: Effect of cryopreservation on fertility rates following ICSI using epididymal spermatozoa

One important indication for intracytoplasmic sperm injection (ICSI) has been in the management of azoospermia due to congenital or acquired causes where ICSI is practiced using surgically retrieved spermatozoa. However, sperm retrieval from either epididymides or testes is a complex procedure, and therefore cryopreservation of supernumerary sperm for future use should be performed in order to avoid the need for repeated sperm retrieval surgeries. This study aimed to evaluate the fertilization rate after ICSI with fresh and frozen-thawed epididymal sperm retrieved from patients with obstructive azoospermia.

A Prospective, Randomized, Double-Blind Study to Compare Two Doses of Recombinant Human Chorionic Gonadotropin in Inducing Final Oocyte Maturity and the Hormonal Profile during the Luteal Phase

Different doses of human chorionic gonadotropin (hCG) have been used in various in vitro fertilization (IVF) treatment protocols to achieve final oocyte maturation. There is as yet no agreement on the optimum dose required. The objective of this study was to compare the effectiveness of 250 and 500 microg recombinant hCG (r-hCG), which represented the lower and upper limits of the dose range, in inducing final oocyte maturation during IVF and intracytoplasmic sperm injection cycles. This was a prospective, randomized, double-blind study. This study was performed at an IVF clinic in a teaching hospital. Sixty patients with an indication for intracytoplasmic sperm injection were studied. The treatment dose used was 250 or 500 microg r-hCG. The percentage of metaphase II oocytes retrieved per patient, as an indicator of oocyte maturation, and the hormone profiles of the treatment cycle starting from the day of hCG up to hCG+10 d were the main outcome measures. The percentage of metaphase II oocytes was similar in the two groups (89.3% vs. 86.0%; P = 0.326) despite higher serum and follicular fluid hCG levels on hCG+2 and hCG+4 d, as was the follicular fluid to serum hCG ratio in the 500-microg r-hCG group. Serum estradiol and progesterone levels were comparable initially, but became significantly higher in the 500-microg r-hCG group on hCG+10 d. The two doses of r-hCG were equally effective in inducing final oocyte maturation. It remains unclear whether the higher midluteal estradiol and progesterone levels in the 500-microg r-hCG group confer any benefit.

Relatively poor oocyte quality is an indication for intracytoplasmic sperm injection

Objective: To determine the relation between the insemination method used and the quality of oocytes and embryos. Design: Prospective study. Setting: Assisted reproductive centers at Yamagata University Hospital and Kuramoto Women’s Clinic in Yamagata, Japan. Patient(s): Forty patients undergoing IVF and 40 patients undergoing intracytoplasmic sperm injection (ICSI). Intervention(s): To estimate oocyte quality, the granulosa cells surrounding the oocyte were fixed and stained with a commercial dye in both groups of patients. One thousand granulosa cells were examined under a fluorescence microscope. Main Outcome Measure(s): The incidence of apoptotic granulosa cells surrounding each oocyte. Result(s): The incidence of apoptosis in the granulosa cells enclosing the oocytes that were fertilized by IVF was significantly lower than that in the oocytes that were fertilized by ICSI. Moreover, the incidence of apoptosis in the granulosa cells enclosing the oocytes that grew into good-quality or fair-quality embryos was significantly lower after conventional IVF than after ICSI. With ICSI, the incidence of apoptosis was not significantly different among the granulosa cells surrounding the oocytes that were inseminated, were fertilized, or developed into good-quality or fair-quality embryos. With IVF, the incidence of apoptosis was highest in the granulosa cells surrounding the oocytes that were inseminated and lowest in the granulosa cells surrounding the oocytes that developed into good-quality and fair-quality embryos. Conclusion(s): A good-quality oocyte is necessary for the development of a good-quality embryo with IVF but not with ICSI. Thus, relatively poor oocyte quality is a good indication for the use of ICSI.

Indications for intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is the latest of several microfertilization techniques that have been utilized predominantly to overcome severe male subfertility, giving fertilization and term pregnancy rates similar to conventional in-vitro fertilization (IVF) (but for other indications). Even though available data on children born after ICSI are very encouraging, the procedure must still be considered as novel and the safety aspect to a great extent unexplored. In our opinion, therefore, ICSI should only be used for specific indications, and in this communication the non-existent, relative and absolute indications for performing ICSI are outlined and discussed. With an apparently normal sperm sample, ICSI should not be used in a first cycle even if only few oocytes are obtained. When there is reason to suspect poor fertilization, ICSI can be used in combination with conventional IVF in a split cycle. This includes cases of 'subnormal' sperm samples, high titres of antisperm antibodies, or following a single cycle of poor fertilization using conventional IVF. Absolute indications for ICSI include two previous fertilization failures with conventional IVF, use of epidiymal or testicular sperm samples, or when only acrosomeless or immotile spermatozoa are available. The fertilization of oocytes prior to preimplantation genetic diagnosis is another absolute indication. It is, however, important to keep in mind that for this novel technique, indications should not be rigid, but remain variable with respect to new findings.

Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro.

The objective of this study was to determine the incidence of DNA fragmentation in human sperm, and to correlate any detected DNA damage with semen analysis parameters and fertilization rates in in vitro fertilization (IVF). A total of 298 semen samples were collected from men in the infertility program at The Toronto Hospital. For each sample, the percentage of sperm with DNA fragmentation was determined using the method of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end-labeling (TUNEL) and fluorescence-activated cell sorting. The percentage of sperm with fragmented DNA was less than 4% in the majority of samples but ranged from 5% to 40% in approximately 27% of the samples. A negative correlation was found between the percentage of DNA fragmentation and the motility, morphology, and concentration of the ejaculated sperm. In 143 IVF samples, a significant negative association was also found between the percentage of sperm with DNA fragmentation and fertilization rate (p = 0.008) and embryo cleavage rate (p = 0.01). In addition, 35 men who smoked demonstrated an increased percentage of sperm with fragmented DNA (4.7 +/- 1.2%) as compared to 78 nonsmokers (1.1 +/- 0.2%; p = 0.01). These results demonstrate a negative association between semen analysis parameters and sperm with fragmented DNA. Since extremely poor semen samples are the indication for intracytoplasmic sperm injection, there is a high likelihood that sperm with fragmented DNA may be selected by chance and used for oocyte injection, resulting in poor fertilization and/or cleavage rates.