Newsletter

Table of Contents

08.02.2007

Newsletter No. 1/2007

Reproductive Medicine

Highly purified HMG versus recombinant FSH in IVF
Cryopreservation and sperm DNA integrity.
A randomized controlled trial of prophylactic antibiotics (co-amoxiclav) prior to embryo transfer.
Cognitive and motor development of 8-year-old children born after ICSI compared to spontaneously conceived children.

1. Highly purified HMG versus recombinant FSH in IVF

BACKGROUND: LH activity may influence treatment response and outcome in IVF cycles.
METHODS: A randomized, assessor-blind, multinational trial compared ongoing pregnancy rates (primary end-point) in 731 women undergoing IVF after stimulation with highly purified menotrophin (HP-hMG) (n = 363) or recombinant FSH (rFSH) (n = 368) following a long GnRH agonist protocol. Patients received identical pre- and post-randomization interventions. One or two embryos were transferred on day 3. RESULTS: More oocytes were retrieved (P < 0.001) after rFSH treatment (11.8) compared with HP-hMG treatment (10.0), but a higher proportion developed into top-quality embryos (P = 0.044) with HP-hMG (11.3%) than with rFSH (9.0%). At the end of stimulation, lower estradiol (E(2)) (P = 0.031) and higher progesterone (P < 0.001) levels were found with rFSH, even after adjusting for follicular response. The distribution of hypo-, iso- and hyper-echogenic endometrium showed a significant (P = 0.023) shift towards the hyperechogenic pattern after rFSH treatment. The ongoing pregnancy rate per cycle was 27% with HP-hMG and 22% with rFSH [odds ratio (95% confidence interval): 1.25 (0.89-1.75)].
CONCLUSION: Superiority of HP-hMG over rFSH in ongoing pregnancy rate could not be concluded from this study, but non-inferiority was established. Pharmacodynamic differences in follicular development, oocyte/embryo quality, endocrine response and endometrial echogenicity exist between HP-hMG and rFSH preparations, which may be relevant for treatment outcome.

Andersen AN, Devroey P, Arce JC. Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Hum Reprod. 2006 Dec;21(12):3217-27. Epub 2006 Jul 27. PMID: 16873892 [PubMed - in process]

2. Cryopreservation and sperm DNA integrity.

Cryopreservation of sperm is an extremely important issue in the field of male infertility as freezing can have detrimental effects on a variety of sperm functions, some of them not accessible to the traditional semen quality analysis. In this study, chromatin structure variations in human spermatozoa in semen were studied with the sperm chromatin structure assay (SCSA), both before and after cryopreservation. Samples were divided into two aliquots: the first was analysed without further treatment, while the second was stored in liquid nitrogen at -196 degrees C using standard cryopreservation techniques. The fresh and thawed aliquots were also assessed by light and fluorescence microscopy (after Acridine Orange staining, AO), and computer-assisted semen analysis (CASA) of motility. Overall sperm quality was found to deteriorate after cryopreservation. When thawed spermatozoa were subjected to an extra swim-up round, a general improvement in nuclear maturity was seen in post-rise spermatozoa.

Gandini L, Lombardo F, Lenzi A, Spano M, Dondero F. Cryopreservation and sperm DNA integrity. Cell Tissue Bank. 2006;7(2):91-8. PMID: 16732411 [PubMed - indexed for MEDLINE

3. A randomized controlled trial of prophylactic antibiotics (co-amoxiclav) prior to embryo transfer.

BACKGROUND: Bacterial contamination of the transfer catheter during embryo transfer is associated with poor clinical outcomes. Antibiotics at the time of embryo transfer may improve outcomes. We evaluated the effect of co-amoxiclav on the rates of bacterial contamination of transfer catheters and clinical pregnancy.
METHODS: On the day of oocyte collection, 350 patients were randomized, with sequentially numbered opaque-sealed envelopes containing treatment allocation assigned randomly by computer, to receive co-amoxiclav on the day before and the day of embryo transfer, or no antibiotics. Following transfer, the catheter tips were cultured and assessed to identify the organism(s) isolated and to quantify the level of the contamination. Couples were followed for 8 weeks to determine whether they had achieved clinical pregnancy. Outcome assessors were blinded to the treatment allocation, and the analysis was by intention to treat.
RESULTS: Antibiotics significantly reduced catheter contamination rates (49.4 versus 62.3%, RR = 0.79, 95% CI: 0.64, 0.97, P = 0.03). There was no difference detected in clinical pregnancy rates between the two groups (36.0 versus 35.5%, P = 0.83) although there was a significant (P = 0.03) association between the level of bacterial contamination and clinical pregnancy rates.
CONCLUSIONS: Co-amoxiclav reduces catheter contamination, but this is not translated into better clinically relevant outcomes such as clinical pregnancy rates. Our findings do not support the routine use of antibiotics at embryo transfer.

Brook N, Khalaf Y, Coomarasamy A, Edgeworth J, Braude P. A randomized controlled trial of prophylactic antibiotics (co-amoxiclav) prior to embryo transfer. Hum Reprod. 2006 Nov;21(11):2911-5. Epub 2006 Jul 10. PMID: 16832124 [PubMed - in process]

4. Cognitive and motor development of 8-year-old children born after ICSI compared to spontaneously conceived children.

BACKGROUND: As a continuation of two large-scale, multicentre studies on the development of 5-year-old ICSI children, we present results of the follow-up study undertaken on the cognitive and motor development of 8-year-old ICSI children.
METHODS: Developmental outcomes of 151 8-year-old singletons born through ICSI after 32 weeks of gestation were compared with those of 153 singletons of the same age born after spontaneous conception (SC). Part of this population was seen in a cohort at the age 5 years. Outcome measures include Wechsler Intelligence Scale for Children-Revised (WISC-R) and Movement Assessment Battery for Children (ABC).
RESULTS: Regarding intellectual functioning, ICSI children tend to obtain significantly higher total (P < 0.01), verbal (P < 0.01) and performance (P < 0.05) intelligence scores than SC children, nevertheless remaining in similar ranges. These effects are small (Cohen's d < 0.50). High maternal educational level stayed in the regression as a factor accounting for some of the variance in total IQ between the groups. In terms of motor development, no significant differences were found between ICSI and SC children regarding overall motor skills, manual, balance and ball skills.
CONCLUSION: In this follow-up study, ICSI and SC children show a comparable cognitive and motor development until the age of 8 years.

Leunens L, Celestin-Westreich S, Bonduelle M, Liebaers I, Ponjaert-Kristoffersen I. Cognitive and motor development of 8-year-old children born after ICSI compared to spontaneously conceived children. Hum Reprod. 2006 Nov;21(11):2922-9. Epub 2006 Aug 2

Gerhard Leyendecker