Intrauterine administration of hCG immediately after oocyte retrieval and the outcome of ICSI: a randomized controlled trial.
Does the intrauterine administration of hCG immediately after oocyte retrieval in antagonist cycles with ICSI and fresh embryo transfer (ET) influence the implantation rate or chemical and clinical pregnancy rates?



The intrauterine administration of hCG after oocyte retrieval increases the implantation rate and chemical and clinical pregnancy rates.



Over half of IVF/ICSI cycles fail due to implantation failure. Intrauterine administration of hCG, a few minutes before ET, increased the implantation and pregnancy rates in most but not in all studies. The effect of intrauterine administration of hCG, after oocyte retrieval, has not yet been studied.



The study was a parallel, triple-blind randomized clinical trial (RCT) performed from September 2015 to February 2016, in a university hospital. We recruited women undergoing antagonist ovarian stimulation, ICSI and ET. For an effect size of 0.2, power of 80% at a significance level of 0.05, we needed 150 participants. Accounting for a 7% dropout rate, a total of 160 women was considered appropriate. A computer-generated randomization list with a block size of 4, with 1:1 allocation was used. The treatment allocation was placed in a sealed, opaque, envelope and picked up consecutively. Immediately after oocyte retrieval, patients in the intervention and control groups were treated with intrauterine injection of hCG and saline, respectively. Participants underwent ET on Day 3. A beta-hCG test was done at 2 weeks. If positive, three transvaginal-ultrasonographies (TVSs) were done at 3, 4 and 10 weeks after ET. The participants were called up thereafter and questioned about the continuity of their pregnancy.



Of 1990 women attending the infertility clinic of our university hospital, 508 were IVF/ICSI candidates during the study period, and 245 of the patients on an antagonist cycle met the criteria to be invited into our trial. Inclusion criteria were normal ovarian reserve, age ≤41, undergoing ICSI, and fresh ET and normal TSH and prolactin. Uncontrolled chronic disease, severe hydrosalpinx, severe endometriosis, morphologic embryo deficiencies, non-obstructive azospermia and high risk of severe ovarian hyperstimulation syndrome were criteria for exclusion. After taking an informed consent, a total of 158 participants were recruited, of which 80 were randomly allocated to receive intrauterine 500 IU hCG in up to 0.5 ml normal saline and 78 to receive intrauterine 0.5 ml normal saline immediately after oocyte retrieval, during general anaesthesia. ICSI was performed conventionally. The 4-8 cell embryos were transferred on the third day after oocyte retrieval. Implantation rate, chemical and clinical pregnancy rates were analysed and compared between the two groups.



Patients' demographic and baseline characteristics were comparable. The clinical results showed statistically significant differences between the two groups regarding the biochemical pregnancy rate (59.2 versus 31.3%; P = 0.001; odds ratio (OR) = 1.88; 95% CI, 1.26-2.82; risk difference (RD) = 27.8; 95% CI, 11.2-42.3), implantation rate (37 versus 17%; P = 0.012; OR = 2.29; 95% CI, 1.02-5.14; RD = 20.2; 95% CI, 5.4-33.8), clinical pregnancy rate (50.7 versus 16.4%; P < 0.001; OR = 3.08; 95% CI, 1.71-5.55; RD = 34.3; 95% CI, 18.7-47.6) and ongoing pregnancy rate (40.1 versus 13.4%; P = 0.001; OR = 3.04; 95% CI, 1.55-5.93; RD = 27.4; 95% CI, 12.7-40.6). The abortion and ectopic pregnancy rates were not statistically different between the two groups.



The insertion of an intrauterine insemination catheter and the injection of a small amount of saline into the uterine cavity (without hCG) may also have some impact on implantation. This effect could be studied by comparing this intervention with another study group without any intrauterine injection.There are no specific side effects mentioned in the literature for the intrauterine administration of hCG, neither were any observed in our study, but it is best to be cautious about probable side effects, because this type of intervention is relatively new and experimental, and deserves more studies before being entered into routine clinical practice.



Intrauterine administration of hCG immediately after oocyte pick up increases its effectiveness; however, further investigations are required before this procedure can be recommended for clinical practice.



This study was supported by the Women's Health Research Center, Tabriz University of Medical Sciences, Iran. No external funds were used. The authors have no conflicts of interest to declare.



IRCT201206165485N4.



2 September 2015.



2 September 2015.
Women's Reproductive Health Research Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran navalin@tbzmed.ac.ir.|Reproductive Medical Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.
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Navali
Women's Reproductive Health Research Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.|Reproductive Medical Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.
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Gassemzadeh
Women's Reproductive Health Research Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.|Reproductive Medical Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.
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Farzadi
Women's Reproductive Health Research Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.|Reproductive Medical Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.
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Abdollahi
Women's Reproductive Health Research Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.|Reproductive Medical Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.
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Nouri
Women's Reproductive Health Research Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.|Reproductive Medical Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.
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Hamdi
Women's Reproductive Health Research Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.|Reproductive Medical Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.
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Mallah
Women's Reproductive Health Research Center, Alzahra University Hospital, Tabriz University of Medical Sciences, Artesh Road, Tabriz 5138665793, Iran.
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Jalilvand
D000328:Adult; D006063:Chorionic Gonadotropin / Q000008:administration & dosage* / Q000627:therapeutic use*; D010064:Embryo Implantation / Q000187:drug effects*; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D054315:Oocyte Retrieval / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods*; D016896:Treatment Outcome; D014599:Uterus / Q000187:drug effects; D055815:Young Adult
D006063:Chorionic Gonadotropin
hCG; implantation rate; intracytoplasmic sperm injection; intrauterine hCG; oocyte retrieval; pregnancy rate