The use of intracytoplasmic sperm injection for the treatment of severe and extreme male infertility

1995 ◽  
Vol 7 (2) ◽  
pp. 237 ◽  
Author(s):  
H Bourne ◽  
N Richings ◽  
O Harari ◽  
W Watkins ◽  
AL Speirs ◽  
...  

The outcome of treatment by intracytoplasmic sperm injection (ICSI) is described for patients with severe male infertility. In 296 consecutive cycles, a normal fertilization rate of 69% was achieved with 288 cycles (97%) resulting in embryos suitable for transfer. A total of 32 clinical pregnancies were achieved from the transfer of fresh embryos (clinical pregnancy rate of 12% per transfer) and an additional 44 clinical pregnancies were obtained after the transfer of frozen-thawed embryos (clinical pregnancy rate of 16% per transfer). Overall, 57 of the 76 pregnancies were ongoing or delivered. An analysis of outcome in 5 male factor subgroups revealed no significant differences in pregnancy and implantation rates between the categories. However, the fertilization rate was significantly lower in patients with oligoasthenoteratozoospermia and significantly higher in those patients for whom epididymal sperm were used for insemination. The treatment of patients with extreme male infertility is also described; normal fertilization and embryo development were obtained using ICSI in patients with mosaic Klinefelter's syndrome, severe sperm autoimmunity, round-headed acrosomeless sperm (globozoospermia), completely immotile sperm selected by hypo-osmotic swelling and sperm isolated from testicular biopsies. Three ongoing pregnancies were obtained from 6 patients for whom testicular sperm were used. These results demonstrate the value of ICSI in the management of severe male infertility, however, the treatment of some types of extreme male infertility using ICSI may be limited.

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Kani M. Falah

Abstract Background The purpose of this study is to compare the outcome of intracytoplasmic sperm injection (ICSI) using fresh sperm versus frozen-thawed sperm in both obstructed and non-obstructed azoospermias. This retrospective study included 159 ICSI cycles from 126 couples. In 91 obstructed azoospermia cases, 66 cycles were treated with fresh testicular sperm and 25 cycles were treated with frozen-thawed testicular samples. In 68 non-obstructed azoospermia cases, 32 cycles were treated with fresh testicular sperm and 36 cycles were treated with frozen-thawed testicular sperm, and the main measure and outcomes calculated are fertilization rate, clinical pregnancy, and live birth rate. Results In case of obstructed azoospermia, there were no statistically significant differences between fresh sperm and frozen-thawed testicular sperm used for ICSI regarding fertilization rate, clinical pregnancy rate, and live birth rate as shown (57%, 47%, 0.093 p value; 23.7%, 17.4%, 0.54 p value; and 11.9%, 8.7%, 0.68 p value, respectively). Non-obstructed azoospermia cases also show no significant differences in fertilization rate (37%, 36%, 0.91 p value), clinical pregnancy rate (20%, 14.3%, 0.58 p value), and live birth rate (4%, 3.6%, 0.93 p value). Conclusion Cryopreservation of testicular sperm is reliable if carried out before ovulation induction especially in cases with non-obstructive azoospermia


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Singh ◽  
R Singh

Abstract Study question What should be the optimal time interval which elapses between oocyte retrieval and denudation followed by ICSI , for optimal results in ART cycles ? Summary answer Our study suggests that an optimum interval between oocyte retrieval and oocyte denudation followed by ICSI, leads to better results in ART cycles. What is known already It is widely accepted that the best timing for OPU is 34–39 hours after ovulation trigger. Some studies suggest that preincubation time before ICSI can be beneficial when it comes to fertilization and pregnancy rates while late ICSI (fertilization) may have negative results due to oocyte ageing. Other studies claim that there is no significant difference in ART results when ICSI is performed between 2–6 hours post Oocyte-Retrieval (OR) . Few studies state that 1–3 hours of COC-culture prior to denudation and oocyte injection is better as far as fertilization , embryo quality and improved oocyte cytoplasmic maturity is concerned. Study design, size, duration RCT of 234 ICSI cycles was carried out between 2017–2019. Patients were divided into two groups-: A- Early denudation with ICSI and B- Late denudation with ICSI.Both the groups were comparable in terms of female age, number of oocytes, day of transfer, number of embryos transferred and embryo quality. Fresh or frozen embryos were transferred , which were always derived from the same stimulation cycle. Exclusion criteria were : Severe male factor / TESA / PESA. Participants/materials, setting, methods 234 ICSI cycles with similar ovarian stimulation protocols were analyzed as per time range between triggering, OPU, denudation and ICSI. Patients were divided into two groups: A- Early denudation (1–2 hours after OPU) with ICSI (1–2 hours after denudation) and B- Late denudation (4–6 hours after Oocyte-Retrieval ) with ICSI (1–2 hours after denudation).Primary outcomes were oocyte maturation and fertilization rates and secondary outcomes were clinical pregnancy rate and abortion rates. Main results and the role of chance In group B ( Late denudation and ICSI), the mean fertilization rate was 67% and the Clinical Pregnancy rate was 46%. This was better than the mean fertilization rate of 56% and clinical pregnancy rate of 39% observed in group A ( Early denudation and ICSI). However the difference was not statistically significant. Therefore, ideal maturation rates were observed when denudation ( followed by ICSI ) was delayed and done 4–6 hours after Oocyte-Retrieval. In ICSI cycles in ART , ovarian stimulation is used to induce the simultaneous growth of multiple follicles, followed by final maturation and ovulation triggering with exogenous hCG. or GnRH-Agonist or both. Generally, oocyte retrieval (OR) is performed 34 - 36h later. In addition, 2–4 hours in culture of the cumulus oocyte complexes (COC) prior to oocyte injection is believed beneficial for fertilization and embryo quality, probably due to improved oocyte cytoplasmic maturity. However, in large ART centers with high workloads, following such definite time intervals is frequently very difficult. Limitations, reasons for caution In large busy centers , maintaining meticulous time intervals is difficult . As our study numbers are small, larger multicentric trials are required in order to confirm our findings and to provide more robust data . This data cannot be applied to IVM, TESE / PESE and severe male-factor infertility. Wider implications of the findings: To achieve a successful fertilization, both nuclear and cytoplasmic maturity are required. Our Study indicates that a slight delay in denudation following Oocyte-Retrieval , will yield a higher number of good quality oocytes. A higher success rate can also be expected due to more number of embryos available for transfer. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
D Se. Sharma

Abstract Study question Male infertility due to idiopathic oligoasthenoteratozoospermia- Does combining Letrozole as antiestrogenic with Coenzyme Q10 as antioxidant give better pregnancy rate ? Summary answer Combination of Co enzyme Q10 with Letrozole can significantly improve semen parameters and outcome of clinical pregnancy rate in idiopathic oligoasthenoteratozoospermic patients. What is known already Elevated levels of reactive oxygen species(ROS) are a major cause of idiopathic male factor infertility which results in sperm membrane lipid peroxidation, DNA damage and apoptosis leading to decrease sperm viability and motility. Antioxidant like Coenzyme Q10 have been used empiricallyin the treatment of oligoasthenozoospermia based on its ability to reverse oxidative stress and sperm dysfunction. Aromatase inhibitor like Letrozolehave been used in idiopathic male infertility by reducing estrogenic effect on spermatogenesis and reducing feedback inhibition of hypothalamopituatarygonadal axis. Thus a therapeutic strategy would need to use supplements to increase sperm energy metabilism, minimise free radical damage. Study design, size, duration Study design: prospective comperative clinical study Primary purpose: treatmenr Size: 60 infertile male attending OPD of SHRISTI HEALTHCARE diagnosed as idiopathic oligoasthenoteratozoospermia Duration: from March2018 to February 2020 Primary outcome: improvement in sperm count, motility and morphology after treatment Secondary outcome: clinical pregnancy rate and live birth rate. Participants/materials, setting, methods Exclusion criteria: Smoker, drug and alcohol abuse, medical treatment with gonadotropin and steroids, varicocele.60 patients were randomisedinto 3 groups. Gr A(N = 20) received Letrozole 2.5mg/day + Co enzyme Q10 300mg/day for 3 months, Gr B(N = 20) received Letrozole 2.5mg/day for 3 months, and Gr C(N = 20) received Coenzyme Q10 300mg/day for 3 months. History taking, general examination, semen analysis, sr.FSH,LH, Testesteron, E2 and scrotal duplex were done for all patients. Main results and the role of chance After treatment, Gr A as compared to Gr B and C showed significant imprivement in all 3 parameters of semen eg sperm count( 3.15±3.38 - 20.9±2.11, p < 0.001), sperm motility( 5.25±3.25 - 42.85±3.30, p < 0.001), sperm morphology( 2.26±7.81 - 25.89±7.05, p < 0.001). Improvement in sperm count and morphology was seen in Gr B(Letrozole gr) but not in sperm motility whereas Gr C ( Co enzyme Q10 gr)showed significant improvement in sperm motility and morphology but not in sperm count. 10 pregnancies occured during follow up period of 1 yr. Clinical pregnancy rate was 30%in Gr A(6/20), 5% in Gr B(1/20), AND 15% in Gr C( 3/20). Live birth rate was 83% in Gr A(5/6), 33.3% inGr C(1/3) whereas sponteneous abortion occured in Gr B pregnancy. Limitations, reasons for caution Limitation of my study was the small sample sizewhich could have some bias in outcome. I did not evaluate DNA fragmentation and level of ROS. Latest evidences report that evaluating ROS can be a diagnostic tool in predictingthe best responder to supplementation. Wider implications of the findings: Majority of studies had investigated the effect of antioxidant and aromatase inhibitor on semen parameter but few concluded their effect on live birth rate. Assisted reproductive techniques are expensive and not universally available, so any pharmacological agent with satisfactory effectiveness should be considered as 1st line treatment of oligoasthenoteratozoospermia. Trial registration number Not applicable


2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
Treasa Joseph ◽  
Mariano Mascarenhas ◽  
Reka Karuppusami ◽  
Muthukumar Karthikeyan ◽  
Aleyamma T Kunjummen ◽  
...  

Abstract STUDY QUESTION Does oral antioxidant pretreatment for the male partner improve clinical pregnancy rate in couples undergoing ART for male factor subfertility? SUMMARY ANSWER There was no significant difference in clinical pregnancy rate following oral antioxidant pretreatment for male partner in couples undergoing ART for male factor subfertility compared to no pretreatment. WHAT IS KNOWN ALREADY Damage to sperm mediated by reactive oxygen species (ROS) contributes significantly to male factor infertility. The ROS-related injury reduces fertilization potential and adversely affects the sperm DNA integrity. Antioxidants act as free radical scavengers to protect spermatozoa against ROS induced damage. During ART, use of sperms which have been exposed to ROS-mediated damage may affect the treatment outcome. Pretreatment with antioxidants may reduce the ROS-mediated sperm DNA damage. Currently, antioxidants are commonly prescribed to men who require ART for male factor subfertility but there is ambiguity regarding their role. STUDY DESIGN, SIZE, DURATION This was an open label, randomized controlled trial conducted at a tertiary level infertility clinic between February 2013 and October 2019. The trial included 200 subfertile couples who were undergoing ART treatment for male factor subfertility. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples were randomized into treatment arm (n = 100) and control arm (n = 100). In the treatment arm, the male partner received oral antioxidants (Vitamin C, Vitamin E and Zinc) for 3 months just prior to the ART cycle. In the control arm, no antioxidant was given to the male partner. The primary outcome was clinical pregnancy rate, while live birth rate (LBR), miscarriage rate and changes in semen parameters were the secondary outcomes. MAIN RESULTS AND THE ROLE OF CHANCE Out of 200 women randomized, 135 underwent embryo transfer as per protocol. Following intention to treat analysis, no significant difference was noted in clinical pregnancy (36/100, 36% vs 26/100, 26%; odds ratio (OR) 1.60, 95% CI 0.87 to 2.93) and LBR (25/100, 25% vs 22/100, 22%; OR 1.18, 95% CI 0.61 to 2.27) between antioxidant and no pretreatment arms. The clinical pregnancy rate per embryo transfer was significantly higher following antioxidant pretreatment (35/64, 54.7% vs 26/71, 36.6%; OR 2.09, 95% CI 1.05 to 4.16) compared to no pretreatment. There was no significant difference in LBR per embryo transfer (25/64, 39.1%, vs 22/71, 31.0%; OR 1.43, 95% CI 0.70 to 2.91) after antioxidant pretreatment versus no pretreatment. The semen parameters of sperm concentration (median, interquartile range, IQR) (18.2, 8.6 to 37.5 vs 20.5, 8.0 to 52.5, million/ml; P = 0.97), motility (median, IQR) (34, 20 to 45 vs 31, 18 to 45%; P = 0.38) and morphology (mean ± SD) (2.0 ± 1.4 vs 2.2 ± 1.5%; P = 0.69) did not show any significant improvement after intake of antioxidant compared to no treatment, respectively. LIMITATIONS, REASONS FOR CAUTION The objective assessment of sperm DNA damage was not carried out before and after the antioxidant pretreatment. Since the clinicians were aware of the group allotment, performance bias cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS The current study did not show any significant difference in clinical pregnancy and LBR following antioxidant pretreatment for the male partner in couples undergoing ART for male subfertility. The findings need further validation in a larger placebo-controlled randomized trial. STUDY FUNDING/COMPETING INTEREST(S) This trial has been funded by Fluid Research grant of Christian Medical College, Vellore (internal funding). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER CTRI/2013/02/003431 TRIAL REGISTRATION DATE 26 February 2013 DATE OF FIRST PATIENT’S ENROLMENT 11 February 2013


2020 ◽  
Vol 35 (6) ◽  
pp. 1411-1420
Author(s):  
Qi Qiu ◽  
Jia Huang ◽  
Yu Li ◽  
Xiaoli Chen ◽  
Haiyan Lin ◽  
...  

Abstract STUDY QUESTION Does an artificially induced FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? SUMMARY ANSWER An additional FSH bolus administered at the time of hCG trigger has no effect on clinical pregnancy rate, embryo quality, fertilization rate, implantation rate and live birth rate in women undergoing the long GnRH agonist (GnRHa) protocol for IVF/ICSI. WHAT IS KNOWN ALREADY Normal ovulation is preceded by a surge in both LH and FSH. Few randomized clinical trials have specifically investigated the role of the FSH surge. Some studies indicated that FSH given at hCG ovulation trigger boosts fertilization rate and even prevents ovarian hyperstimulation syndrome (OHSS). STUDY DESIGN, SIZE, DURATION This was a randomized, double-blinded, placebo-controlled trial conducted at a single IVF center, from June 2012 to November 2013. A sample size calculation indicated that 347 women per group would be adequate. A total of 732 women undergoing IVF/ICSI were randomized, using electronically randomized tables, to the intervention or placebo groups. Participants and clinical doctors were blinded to the treatment allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients aged ≤42 years who were treated with IVF/ICSI owing to tubal factor, male factor, unexplained, endometriosis and multiple factors were enrolled in this trial. Subjects all received a standard long GnRHa protocol for IVF/ICSI and hCG 6000–10 000 IU to trigger oocyte maturation. A total of 364 and 368 patients were randomized to receive a urinary FSH (uFSH) bolus (6 ampules, 450 IU) and placebo, respectively, at the time of the hCG trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were FSH level on the day of oocyte retrieval, number of oocytes retrieved, good-quality embryo rate, live birth rate and rate of OHSS. MAIN RESULTS AND THE ROLE OF CHANCE There were no significant differences in the baseline demographic characteristics between the two study groups. There were also no significant differences between groups in cycle characteristics, such as the mean number of stimulation days, total gonadotrophin dose and peak estradiol. The clinical pregnancy rate was 51.6% in the placebo group and 52.7% in the FSH co-trigger group, with an absolute rate difference of 1.1% (95% CI −6.1% to 8.3%). The number of oocytes retrieved was 10.47 ± 4.52 and 10.74 ± 5.01 (P = 0.44), the rate of good-quality embryos was 37% and 33.9% (P = 0.093) and the implantation rate was 35% and 36% (P = 0.7) in the placebo group and the FSH co-trigger group, respectively. LIMITATIONS, REASONS FOR CAUTION This was a single-center study, which may limit its effectiveness. The use of uFSH is a limitation, as this is not the same as the natural FSH. We did not collect follicular fluid for further study of molecular changes after the use of uFSH as a co-trigger. WIDER IMPLICATIONS OF THE FINDINGS Based on previous data and our results, an additional FSH bolus administered at the time of hCG trigger has no benefit on clinical pregnancy rates in women undergoing the long GnRHa protocol in IVF/ICSI: a single hCG trigger is sufficient. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China (2016YFC1000205); Sun Yat-Sen University Clinical Research 5010 Program (2016004); the Science and Technology Project of Guangdong Province (2016A020216011 and 2017A020213028); and Science Technology Research Project of Guangdong Province (S2011010004662). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-12002246). TRIAL REGISTRATION DATE 20 May 2012. DATE OF FIRST PATIENT’S ENROLMENT 10 June 2012.


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