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23.03.2007
 
Newsletter No. 2/2007
 
Reproductive Medicine
  1. Impact of fresh-cycle variables on the implantation potential of cryopreserved-thawed human embryos.
  2. Role of gonadotropin-releasing hormone antagonists in poor responders.
  3. Outcome of in vitro fertilization in women 45 years and older who use autologous oocytes.
  4. Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome.

1. Impact of fresh-cycle variables on the implantation potential of cryopreserved-thawed human embryos.

OBJECTIVE: To compare the clinical outcomes of cryopreservation according to the indications for freezing and the outcomes of the fresh cycle from which the embryos were derived.
DESIGN: Retrospective study.
SETTING: Private assisted-reproduction unit.
PATIENT(S): Three thousand, three hundred and sixty-eight embryos in 702 frozen-thawed embryo transfer (ET) cycles.
INTERVENTION(S): Clinical outcomes of frozen-thawed ET cycles in which embryos were derived from fresh conception cycles (n = 436), from fresh nonconception cycles (n = 180), or where the fresh cycle was cancelled due to impending ovarian hyperstimulation syndrome (OHSS) (n = 86).
MAIN OUTCOME MEASURE(S): Cryosurvival, clinical pregnancy, and implantation rates.
RESULT(S): Despite similar cryosurvival rates and the transfer of a similar number of embryos, significantly higher clinical pregnancy and implantation rates were obtained in the fresh-conception and OHSS groups. The implantation potential of frozen-thawed embryos that were not selected in a prior fresh cycle was comparable to that of embryos selected for fresh transfer.
CONCLUSION(S): The success of frozen-thawed ET depends on the outcome of fresh ET and the indications for cryopreservation. Success is similar to that of fresh ET cycles in patients who had all their embryos frozen due to impending OHSS.

Reference

Urman B, Balaban B, Yakin K, Impact of fresh-cycle variables on the implantation potential of cryopreserved-thawed human embryos. Fertil Steril. 2007 Feb;87(2):310-5. Epub 2006 Nov 13. PMID: 17097088 [PubMed - indexed for MEDLINE]

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2. Role of gonadotropin-releasing hormone antagonists in poor responders.

OBJECTIVE: To evaluate the role of GnRH antagonists in poor-responder protocols. DESIGN: Literature review. CONCLUSION(S): The optimum stimulation protocol for poor responders is unknown. Although many IVF programs currently use GnRH antagonists for poor responders, there have been only four prospective, randomized trials comparing GnRH antagonists to alternate protocols. None of these studies had sufficient power to evaluate a difference in pregnancy rates (PRs), and in all four cases, IVF outcomes were comparable. Nevertheless, interest in the use of GnRH antagonists in poor responders has continued. GnRH antagonists may be associated with simpler stimulation protocols, lower gonadotropin requirements, reduced patient costs, and shorter downtimes between consecutive cycles. However, the greatest advantage of GnRH antagonists may lie in the ability to assess ovarian reserves immediately prior to deciding whether or not to initiate gonadotropin stimulation. The ability to respond to cycle-to-cycle variation in antral follicle counts may allow the optimization of oocyte yield and reduce cycle cancellation rates. It remains to be seen if this approach (initiating gonadotropins only in cycles where an adequate antral follicle count is present) also translates into higher clinical PRs for poor responders.

Reference

Mahutte NG, Arici A, Role of gonadotropin-releasing hormone antagonists in poor responders. Fertil Steril. 2007 Feb;87(2):241-9. Epub 2006 Nov 16. Review. PMID: 17113088 [PubMed - indexed for MEDLINE

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3. Outcome of in vitro fertilization in women 45 years and older who use autologous oocytes.

OBJECTIVE: To determine the IVF outcome in women over the age of 44 years.
DESIGN: Retrospective analysis.
SETTING: University-based IVF center.
PATIENT(S): Two hundred eighty-eight consecutive IVF cycles in women over the age of 44 years.
INTERVENTION(S): IVF. MAIN OUTCOME MEASURE(S): Ovarian response and cycle outcome.
RESULTS: The mean age of the patients was 45.4 (+/-0.73) years, with a range of 45-49 years. Fifty-seven of 288 (19.8%) did not start because of an elevated FSH or ovarian cyst. Just over 30% (70/231) had their cycle cancelled before retrieval. The mean number of oocytes was 6.8 (+/-3.8), and the mean number of fertilized zygotes was 5.4 (+/-3.4). On average, the mean numbers of embryos replaced were 3.2 (+/-1.5). An overall pregnancy rate of 21.1% (34/161) per retrieval was found. Of these, 85.3% (29/34) experienced a pregnancy loss. The overall delivery rate was 3.1% (5/161) per retrieval. Only patients at 45 years of age with a good response (>5 oocytes) achieved a delivery.
CONCLUSION(S): We have shown that IVF is a reasonable option for women of very advanced maternal age (>44 years) but is limited to those at the age of 45 years with a response of >5 oocytes.

Reference

Spandorfer SD, Bendikson K, Dragisic K, Schattman G, Davis OK, Rosenwaks Z. Outcome of in vitro fertilization in women 45 years and older who use autologous oocytes. Fertil Steril. 2007 Jan;87(1):74-6. PMID: 17197285 [PubMed - indexed for MEDLINE]

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4. Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome.

OBJECTIVE: To determine which first-line medication is more effective in polycystic ovary syndrome (PCOS) patients for ovulation induction and pregnancy achievement and to verify whether any patient characteristic is associated with a better response to therapy. DESIGN: Observational comparative study.
SETTING: Fertility clinic.
PATIENT(S): One hundred fifty-four infertile women with oligomenorrhea and hyperandrogenism.
INTERVENTION(S): Group 1 (56 patients) received clomiphene citrate (CC) 50 mg from days 5-9 of the cycle. Group 2 (57 patients) received 500 mg of metformin 3 times a day. Group 3 (41 patients) received both medications.
MAIN OUTCOME MEASURE(S): Ovulation and pregnancy.
RESULT(S): Patients receiving metformin alone had an increased ovulation rate compared with those receiving CC alone (75.4% vs. 50%). Patients on metformin had similar ovulation rates compared with those in the combination group (75.4% vs. 63.4%). Pregnancy rates were equivalent in the 3 groups. Response to metformin was independent of body weight and dose. Finally, nonsmoking predicted better ovulatory response overall as well as lower fasting glucose for CC and lower androgens for metformin.
CONCLUSION(S): Metformin is better for ovulation induction than CC alone and equivalent for pregnancy achievement. We suggest that metformin can be used first for ovulation induction in patients with PCOS regardless of their weight and insulin levels because of its efficacy and known safety profile.

Reference

Neveu N, Granger L, St-Michel P,Lavoie HB. Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome. Fertil Steril. 2007 Jan;87(1):113-20. Epub 2006 Nov 1. PMID: 17081535 [PubMed - indexed for MEDLINE

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Gerhard Leyendecker