- Urinary hMG versus recombinant FSH
- Single blastocyst transfer
- Fast cleaving embryos
- Polycystic ovarian disease induced by pulsatile GnRH
- Ovarian protection during chemotherapy.
1. Urinary hMG versus recombinant FSH
BACKGROUND: Since the most recent Cochrane review on hMG versus rFSH for controlled ovarian hyperstimulation following a long down-regulation protocol, several new trials have emerged. METHODS: We conducted a systematic review and meta-analysis of randomized trials comparing the effectiveness of hMG versus rFSH following a long down-regulation protocol in IVF-ICSI cycles, on the primary outcome of live birth per woman randomized, as well as several other secondary outcomes. Searches were conducted in MEDLINE, EMBASE, Science Direct, Cochrane Library and databases of abstracts (last search January 2007). RESULTS: Seven randomized trials, consisting of a total of 2159 randomized women, were identified. A meta-analysis of these trials showed a significant increase in live birth rate with hMG when compared with rFSH (relative risk, RR = 1.18, 95% CI: 1.02-1.38, P = 0.03). The heterogeneity test was non-significant (P = 0.97), suggesting that there was no statistical inconsistency between the seven studies. The pooled risk difference (RD) for the outcome of live birth rate was 4% (95% CI: 1-7%) for these study populations. There was an increase in clinical pregnancy rates with hMG when compared with rFSH (RR = 1.17, 95% CI 1.03-1.34). No significant differences were noted for gonadotrophin use, spontaneous abortion, multiple pregnancy, cancellation and ovarian hyperstimulation syndrome rates. CONCLUSIONS: For the populations in the randomized trials, hMG was associated with a pooled 4% increase in live birth rate when compared with rFSH in IVF-ICSI treatment following a long down-regulation protocol.
Coomarasamy A, Afnan M, Cheema D, van der Veen F, Bossuyt PM, van Wely M.
Urinary hMG versus recombinant FSH for controlled ovarian hyperstimulation following an agonist long down-regulation protocol in IVF or ICSI treatment: a systematic review and meta-analysis
Hum Reprod. 2008 Feb;23(2):310-5. Epub 2007 Dec 3
2. Single blastocyst transfer
OBJECTIVE: To examine the clinical pregnancy rate (CPR) and multiple pregnancy rate (MPR) in a large in vitro fertilisation (IVF) programme before and after the introduction of single blastocyst transfer (SBT) strategy in a selected group of women. DESIGN: A 3-year pre- and postintervention study. SETTING: A tertiary reproductive medicine and assisted conception unit in a London teaching hospital. POPULATION: Two thousand four hundred and fifty-one fresh IVF cycles performed between July 2004 and June 2007 at the Assisted Conception Unit at Guyâ€™s and St Thomasâ€™ Hospital NHS Foundation Trust were included in the study. METHODS: In January 2006, we implemented a multidisciplinary intervention involving the introduction of a selective day 5 SBT service together with an educational programme on the risks of multiple pregnancy and potential advantages of blastocyst transfer aimed at couples at high risk of multiple pregnancy. MAIN OUTCOME MEASURES: The CPR per cycle started and MPR per clinical pregnancy achieved. RESULTS: A statistically significant increase in the CPR from 27% (324/1198) to 32% (395/1253) (risk difference [RD] 5%, risk ratio [RR] 1.17, 95% CI 1.03-1.32, P= 0.015) and reduction in the MPR per clinical pregnancy from 32% (103/272) to 17% (69/395) (RD 15%, RR 0.46, 95% CI 0.35-0.60, P < 0.001) were observed after introduction of the SBT service. CONCLUSION: Selective SBT in women with good prognosis can reduce the MPR after IVF while maintaining the overall success rate of the IVF programme.
Khalaf Y, El-Toukhy T, Coomarasamy A, Kamal A, Bolton V, Braude P.
Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study.
BJOG. 2008 Feb;115(3):385-90.
3. Fast cleaving embryos
OBJECTIVE: To evaluate developmental potential of fast cleaving day 3 embryos. DESIGN: Retrospective analysis. SETTING: Academic reproductive center. PATIENT(S): Three thousand five hundred twenty-nine embryos. INTERVENTION(S): Day 3 embryos were classified according to cell number: slow cleaving: or=10 cells, and further evaluated on day 5. The preimplantation genetic diagnosis (PGD) results of 43 fast cleaving embryos were correlated to blastocyst formation. Clinical outcomes of transfers involving only fast cleaving embryos (n = 4) were evaluated. MAIN OUTCOME MEASURE(S): Blastocyst morphology correlated to day 3 blastomere number. Relationship between euploidy and blastocyst formation of fast cleaving embryos. Implantation, pregnancy (PR), and birth rates resulting from fast embryo transfers. RESULT(S): Blastocyst formation rate was significantly greater in the intermediate cleaving (72.7%) and fast cleaving (54.2%) groups when compared to the slow cleaving group (38%). Highest quality blastocysts were formed significantly more often in the fast cleaving group. Twenty fast cleaving embryos that underwent PGD, formed blastocysts, of which 45% (9/20) were diagnosed as euploid. Aneuploidy was diagnosed in 82.6% (19/23) of arrested embryos. A 50% implantation and 100% PR and birth rate were achieved with embryo transfers involving fast cleaving embryos. CONCLUSION(S): Fast cleaving embryos not only reach the blastocyst stage at a similar rate to intermediate cleaving embryos, but also exceed morphological quality criteria on day 5. Fast cleaving embryo transfers demonstrated a high clinical potential.
Luna M, Copperman AB, Duke M, Ezcurra D, Sandler B, Barritt J.
Human blastocyst morphological quality is significantly improved in embryos classified as fast on day 3 (>or=10 cells), bringing into question current embryological dogma.
Fertil Steril. 2008 Feb;89(2):358-63. Epub 2007 May 25
4. Polycystic ovarian disease induced by pulsatile GnRH
OBJECTIVE: To present the observation in six out of 120 women treated with pulsatile GnRH for ovulation induction, who developed hyperandrogenemia and polycystic ovaries during treatment. DESIGN: Clinical observation. SETTING: Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Austria. PATIENT(S): A total of 120 women initially diagnosed as suffering from primary or secondary hypothalamic amenorrhea were treated for ovulation induction with pulsatile administration of GnRH for up to 140 days. There was no indication of the presence of polycystic ovaries or hyperandrogenemia before therapy. INTERVENTION(S): Pulsatile GnRH therapy using the Zyklomat pump. MAIN OUTCOME MEASURE(S): Ovulatory menstrual cycles. RESULT(S): Initially, all patients responded to pulsatile GnRH administration with ovulation and corpus luteum formation. During continuation of treatment, 6 patients developed an increase in LH and LH/FSH ratio as well as a progressive rise in serum T levels resulting in hyperandrogenemia. This was accompanied by the development of polycystic ovaries and cessation of follicular maturation. CONCLUSION(S): We conclude from these observations that restoration of normal GnRH stimulation of the pituitary gland can result in the development of hyperandrogenemia and polycystic ovaries, suggesting a pituitary or ovarian defect underlying the pathogenesis of this disorder.
Mattle V, Bilgyicildirim A, Hadziomerovic D, Ott HW, Zervomanolakis I, Leyendecker G, Wildt L.
Polycystic ovarian disease unmasked by pulsatile GnRH therapy in a subgroup of women with hypothalamic amenorrhea.
Fertil Steril. 2008 Feb;89(2):404-9. Epub 2007 Jun 21
5. Ovarian protection during chemotherapy
OBJECTIVE: To minimize the gonadotoxic effect of chemotherapy by the cotreatment with a GnRH agonistic analogue (GnRH-a). DESIGN: Prospective nonrandomized study with concurrent and historical controls. SETTING: University medical center. PATIENT(S): One hundred fifteen female patients with Hodgkin lymphoma (HL). INTERVENTION(S): Sixty-five patients received a monthly injection of GnRH-a, administered before starting chemotherapy until its conclusion, up to a maximum of 6 months. Thirty-five patients were treated with ABVD and 76 with a procarbazine-containing regimen. This group was compared with a control group of 46 women who were treated concurrently with similar chemotherapy (n = 26) without GnRH-a or were historical controls (n = 20). MAIN OUTCOME MEASURE(S): Cyclic ovarian function (COF) versus premature ovarian failure (POF). RESULT(S): The ovarian function could be determined in 111 patients. In the GnRH-a/chemotherapy group, 63 out of 65 patients resumed ovulation and regular menses (96.9 %), compared with 63% of the 46 control subjects. Twenty of the 22 patients in the BEACOPP/escalated BEACOPP/GnRH-a cotreatment resumed cyclic ovarian function versus 9 of the 14 in the chemotherapy-only group. All 17 MOPP/ABV/GnRH-a cotreated patients resumed COF versus 11 of the 22 in the chemotherapy-only group. There was no significant effect of the GnRH-a cotreatment regarding COF in the ABVD group. There were no significant differences in the cumulative doses of the various alkylating agents between the two groups. CONCLUSION(S): Cotreatment with GnRH-a may reduce ovarian damage significantly in female patients treated for HL and should be considered in addition to assisted reproduction for women in reproductive age receiving gonadotoxic chemotherapy.
Blumenfeld Z, Avivi I, Eckman A, Epelbaum R, Rowe JM, Dann EJ.
Gonadotropin-releasing hormone agonist decreases chemotherapy-induced gonadotoxicity and premature ovarian failure in young female patients with Hodgkin lymphoma.
Fertil Steril. 2008 Jan;89(1):166-73. Epub 2007 Jun 28.