Archived Comments for: Intrauterine administration of human chorionic gonadotropin does not improve pregnancy and life birth rates independently of blastocyst quality: a randomised prospective study

Wrong data in Table 5 and possible error on interpreting the hCG effect

27 July 2015

This is a great work but needs correcting the Table 5 and should have avoided interpreting some aspect of the hCG effect.

Table 5 : wrong results from Reference 27

Reference 27 Hong et al., Correct Results

Result(s): A total of 473 blastocysts were transferred into 300 patients. There were no differences between the two groups in sustained implantation rate (48.1% in the hCG group, 44.2% in the control group) or ongoing pregnancy rate (58.8% in the hCG group, 52.0% in the control group).

Also please note that most of the published data on hCG injection/infusion prior to/during or following embryo transfer were done in stimulation cycle with fresh embryo.

 Unlike the authors of this manuscript, Hong et al did not report that embryo culture media containing hCG had a consistent negative effect on the Pregnancy outcome.

 This night suggest the hCG used for improving the pregnancy outcome could have toxic effect on embryo and uterine endometrium. The clinical trials should use recombinant or very highly purified hCG.

For Example please see the Abstract below:

Purification of Human Chorionic Gonadotropin (hCG) for Intrauterine Injection. A. M. Rosen,a M. C. Hermoso,b H. Cook-Andersen,c D. de Ziegler,d D. R. Meldrum.b aAlbany Medical College, Albany, NY, USA; bReproductive Partners Medical Group, Redondo Beach, CA, USA; cDepartment of Reproductive Medicine, University of California San Diego, San Diego, CA, USA; dDepartment of Reproductive Endocrinology and Infertility, Universit_e Paris Descartes, Paris, France.

BACKGROUND: Recent research showed that intrauterine injection of hCG before embryo transfer resulted in significantly increased embryo implantation. (1) Purification of hCG may allow for maximal benefit.

OBJECTIVE(S): The purpose of this study was to evaluate a filtration protocol that would retain hCG concentration and bioactivity while allowing for improved mouse embryo development to the blastocyst stage when compared with unfiltered preparations.

MATERIALS AND METHOD(S): A simple and inexpensive size-exclusion membrane was used to purify hCG and the product was evaluated using in vitro and in vivo assays. HCG was dissolved at 500 IU per 40 uL in Vitrolife G2 Plus, placed in an Amicon Ultra-15 (3K) filter, diluted 20-fold with G-Rinse, centrifuged for 1 hour at 4,000 RPM, and reconstituted in G2 Plus. Bioactivity was assessed by injecting 10 IU of hCG into female mice to induce ovulation in vivo. Two-cell mouse embryos were cultured in mediawith 500 IU per 40 uL of filtered or unfiltered hCG to test viability of the embryos. Osmolarity, pH, and hCG concentration of the preparations were also measured.

RESULT(S): Before purification, hCG arrested growth of mouse embryos at the cleavage stage. Purification of hCG resulted in marked improvements in blastocyst development (from 0% to >90%). HCG retained bioactivity after purification as assessed by stimulation of ovulation in mice. After purification, improvements in osmolarity (from 431 to 293 milliosmoles/L) and pH (from

6.7 to 7.4) were observed. Over 92% of the hCG was recovered after purification (range 85-109%). Testing of vial rinse showed high embryo viability

TABLE. (mean of similar values using 10 vials from three manufacturers; 1.

Unfiltered 2. Filtered)

Osmolarity                 hCG conc                     Bioactivity Assay:     Toxicity Assay

oocytes/mouse       (mIU/ml)                  number of fertilized        Cleaved embryos

mOsm/kg)                                                                                            reaching   blastocyst (%)

1.      431                103,7 97                                  15.4                          0/60 = 0%

2.      293             95,629 (92% recovery)            16.2                          84/90 = 93%

The pH before and after processing was estimated at 6.7 and 7.4 respectively. After removing the reconstituted hCG from the vial, a further rinse

of the vial with media failed to detect any embryo toxicity using one-cell mouse embryos (% blast¼ 100).

CONCLUSION(S): While hCG reconstituted in media was highly toxic to mouse embryos, purified hCG allowed a high rate of blastocyst development. Embryo toxicity was due to additional solutes in the hCG powder and possibly to contaminants introduced during processing, but not to toxicity of the vial or the rubber stopper. This simple and inexpensive technique to purify hCG should further improve the already demonstrated enhancement of embryo implantation with intrauterine injection.

SUPPORT: None.

Reference

1. Mansour R, Tawab N, Kamal O, El-Faissal Y, Serour A, Aboulghar M, Serour G. Intrauterine injection of human chorionic gonadotropin before embryo transfer significantly improves the implantation and pregnancy rates in in vitro fertilization/intracytoplasmic sperm injection:a prospective randomized study. Fertil Steril 2011;96:1370–4.

Competing interests