Oocyte donation programs: strategy for improving results.

Oocyte donation is now a useful option for women who cannot start a spontaneous pregnancy for reasons related to advanced age, iatrogenic factors, early depletion of ovarian reserve, or genetic disorders. Embryo implantation rates, pregnancy rates, and pregnancy outcomes among women included in oocyte donation programs were shown to be comparable to those of spontaneous or in vitro fertilization (IVF) pregnancies. With oocyte freezing and cryobanks, recipients may have a successful response to oocyte donation, with no need to be on waiting lists, access to a larger number of oocytes from the same donor, and a lesser risk of infectious disease transmission.

Effect of piroxicam administration before embryo transfer on IVF outcome: a randomized controlled trial.

Two hundred women aged between 28 and 43 years, with infertility from tubal, male, endometriosis or unexplained factor were randomly allocated into treatment (100 patients) and control (100 patients) groups. On the day after oocyte retrieval, each patient began supplementation with progesterone 8% vaginal gel, once daily. The patients in the treatment group received a single oral dose of 10 mg of the non-steroidal anti-inflammatory drug piroxicam 1-2 h before embryo transfer. No statistically significant difference was found between the two groups in any of the analysed endpoints. The rate of positive beta-human chorionic gonadotrophin test per transfer was 37% in the women treated with piroxicam and 47% in controls. The clinical pregnancy rate per transfer and implantation rate were 34% and 19.2% with piroxicam, 38% and 21.9% in controls. The miscarriage rate was 11.8% and 13.2%. No beneficial effect of piroxicam on pregnancy rates was found evaluating either different infertility causes or different ages. This study shows that the administration of a single dose of piroxicam before embryo transfer has no additional effect on pregnancy outcome in patients receiving adequate doses of progesterone for luteal phase supplementation after IVF or ICSI.

Inadvertent recombinant human follicle stimulating hormone bolus instead of human chorionic gonadotrophin leads to the retrieval of competent oocytes in IVF program.

OBJECTIVE: To present a case where recombinant human FSH (r-hFSH) was accidentally used instead of hCG and resulted in oocyte maturation. DESIGN: Case report. SETTING: A tertiary infertility center. PATIENT(S): A 36-year-old woman underwent IVF for infertility problems. The couple was unable to obtain a pregnancy during the previous 2 years. INTERVENTION(S): Oocyte retrieval after a r-hFSH bolus (two vials of Gonal-F 1050 IU) instead of the routinely used hCG. MAIN OUTCOME MEASURE(S): Oocyte maturity evaluation, fertilization after intracytoplasmic sperm injection, cleavage stage, and embryo quality. RESULT(S): A total of nine oocytes were retrieved; eight were metaphase II. Three eggs were fertilized by intracytoplasmic sperm injection, and four of the remaining MII oocytes were cryopreserved. All three oocytes fertilized and developed to three good-quality embryos that were transferred on day 2. No pregnancy was obtained from this fresh transfer cycle or from transferred embryos resulting from the thawing cycle. CONCLUSION(S): A massive r-hFSH administration can lead to the retrieval of mature MII oocytes that are able to fertilize and give good-quality embryos to transfer.

Comparison of IVF and ICSI when only few oocytes are available for insemination.

The aim of this work was to evaluate the efficiency of IVF and intracytoplasmic sperm injection (ICSI) when few eggs available for insemination. A total of 601 women (group A, mean age 31.2 +/- 2.8 years) who were undergoing a total of 671 assisted reproduction cycles donated their excess oocytes to 694 patients (group B, mean age 41.0 +/- 0.2) for 1606 replacement cycles. Each recipient received three to five eggs. The recipients were divided into two groups depending on the insemination method used (IVF, group B1; or ICSI, group B2); ICSI patients were then subdivided into two further groups based on the semen parameters: B2A adequate for IVF and B2B only suitable for ICSI. The results showed that, when comparing A versus B and B1 versus B2, no significant differences were found in terms of pregnancy (28.0 versus 24.1% and 25.5 versus 21.4%), implantation (15.6 versus 14.9% and 15.9 versus 13.1%) and miscarriage (15.4 versus 20.5% and 17.9 versus 26.3) rates respectively. Comparing subgroups B2A and B2B, no significant differences were found in terms of pregnancy (20.0 versus 21.9%), implantation (14.4 versus 12.7%) and miscarriage rates (18.2 versus 28.6%) respectively. In conclusion, ICSI does not seem to yield better outcomes.

Anomalies in sperm chromatin packaging: implications for assisted reproduction techniques.

Sperm protamine deficiency and DNA damage were analysed employing chromomycin A(3) (CMA(3)) staining and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay, respectively, in 132 patients (82 IVF, 50 intracytoplasmic sperm injection [ICSI]). The antioxidant ability of seminal plasma was analysed in 10 men, using the total oxidant scavenging capacity assay. A significant negative correlation was found between abnormal protamination and sperm parameters, including sperm DNA fragmentation (P < 0.01). A close relationship was found between sperm protamination and fertilization and pregnancy only in IVF (P = 0.004 and P < 0.04, respectively); in ICSI there was a correlation between DNA fragmentation and pregnancy (P = 0.031). Finally, there was a negative correlation between chromatin under-protamination and the antioxidant ability of seminal plasma (P < 0.01). Results of this study underline that, despite sperm abnormal protamination and DNA fragmentation being positively correlated, they affect the reproductive outcome in different ways: in particular there was good prognostic value for CMA(3) analysis only in IVF, whereas DNA fragmentation analysis was prognostic only for ICSI outcome. Data are also provided to support the idea of a relationship between defective antioxidant system activity and impairment of chromatin packaging.

Vaginal gel versus intramuscular progesterone for luteal phase supplementation: a prospective randomized trial.

The aim of this randomized study was to compare the efficacy of intramuscular progesterone (IMP) and progesterone in vaginal gel (VGP) at two different doses for luteal support in IVF. A total of 412 patients, aged between 28 and 37 years, were randomized into three groups. The day after oocyte retrieval each patient began supplementation with one of the following: IMP 50 mg daily (150 patients), VGP 90 mg once daily (143 patients), or VPG 90 mg twice daily (148 patients). No significant difference was found between the three groups in any of the endpoints. The rate of positive beta-human chorionic gonadotrophin per transfer was 38.4% with IMP, 35.0% with VPG once daily and 43.1% with VPG twice daily. Clinical pregnancy rate per transfer and implantation rate were 32.6% and 19.6% with IMP, 26.3% and 16.4% with one dose of VGP, and 37.2% and 21.1% with two doses of VGP. Live birth rate per transfer was 26.1%, 23.4% and 29.9%, respectively. Progesterone vaginal gel can be successfully used as an alternative to intramuscular progesterone for luteal support in IVF. One daily dose appears sufficient to induce clinical pregnancies and live births at a rate comparable to intramuscular supplementation.

Live birth after IVF in a 46-year-old woman.

Pregnancies after IVF have been reported in women aged > or =44 years, but nobody older than 45 years at oocyte retrieval delivered. We report a case of birth of a healthy child after IVF in a 46-year-old infertile woman. Ovarian stimulation was performed with clomiphene citrate, 150 mg daily for 5 days. Three oocytes were retrieved and one embryo was replaced. The patient delivered a healthy male infant after Caesarean section at 39 weeks. A successful pregnancy after IVF with homologous oocytes can be achieved in women older than 45 years. At this age IVF is not a cost-effective treatment compared with oocyte donation, but it may be offered in countries in which gamete donation is forbidden.

Tailoring FSH and LH administration to individual patients.

Many clinical trials have been carried out to find the optimal gonadotrophin starting dose for IVF. The consensus for patients undergoing first treatment and <40 years old is a range stretching from 150 to 250 IU/day. The varying ovarian response to gonadotrophins may be due to factors such as age, basal FSH, number of antral follicles and body mass index, all of which should be taken into account before choosing the type of protocol and the amount of gonadotrophins to use. Increasing the dose of recombinant FSH does not compensate for the age-related decline in retrievable oocytes. Higher doses of gonadotrophins are required in overweight patients, but enhanced protocols are thought to only marginally improve live birth rates in obese women. The actual role of LH in controlled ovarian stimulation is still a matter of debate. A therapeutic 'window' of LH concentrations, below which oestradiol production is inadequate and above which LH may be detrimental to follicular development has been described.

Use of antagonists in ovarian stimulation protocols.

Gonadotrophin-releasing hormone (GnRH) antagonists have been introduced in IVF to prevent premature LH surge. They bind competitively to pituitary receptors and prevent endogenous GnRH from exerting any stimulus on pituitary cells, avoiding the initial 'flare-up' effect and decreasing gonadotrophin secretion within a few hours. Pituitary reserve and gonadotrophin synthesis are not affected; therefore, the recovery of pituitary function is rapid. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day 6-7 of stimulation, or when the leading follicle is 14-15 mm, until human chorionic gonadotrophin (HCG) administration. The single-dose protocol involves the single administration of 3 mg cetrorelix on day 7-8 of stimulation. Both antagonists with either regimen seem to be equally effective in the prevention of the LH surge. Compared with a long luteal agonist protocol, the treatment is shorter and requires a smaller amount of gonadotrophins. Pregnancy rate seems to be lower, but a decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) is reported by several studies. A promising aspect of antagonists may be the possibility of making treatment less aggressive. Finally, in antagonist cycles, ovulation triggering is possible by GnRH agonists, avoiding the deleterious effect of HCG and thus preventing OHSS.

Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist.

OBJECTIVE: To test the efficacy of endometrial preparation with exogenous steroids, without pretreatment with gonadotropin-releasing hormone (GnRH) agonist, in women with normal ovarian function. DESIGN: Prospective randomized study. SETTING: Private outpatient infertility clinic. PATIENT(S): Two hundred ninety-six women undergoing frozen-thawed embryo transfer. INTERVENTION(S): In group 1 (146 patients), depot GnRH agonist was administered in the luteal phase; treatment with 17beta-estradiol transdermal patches at steadily increasing dosage from 100 to 300 microg was then given for at least 12 days. In group 2 (150 patients), endometrial preparation began on day 1 of menstrual cycle. The starting dose was 200 microg; this was increased to 300 microg after 7 days. MAIN OUTCOME MEASURE(S): Pregnancy, abortion, implantation and cancellation rates. RESULT(S): In group 2, six cycles (4%) were cancelled due to evidence of ovulation. Groups were similar in the percentage of embryos that survived freezing-thawing (77.1% in group 1 and 76.6% in group 2) and in the number of embryos transferred per patient (2.1 +/- 0.6 and 2.1 +/- 0.7, respectively). Groups 1 and 2 did not differ significantly in rates of pregnancy (19.7% and 24.1%), abortion (17.8% and 11.7%), and implantation (10.4% and 11.9%). CONCLUSION(S): Endometrial preparation for frozen-thawed embryo transfer based exclusively on steroid administration appears to be as effective as the more conventional protocol involving preliminary desensitization with a GnRH agonist. This simplified protocol reduces costs, minimizes pharmacologic treatment, and increases patient compliance.