Luca Dal Prato

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.

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.

Comparison between depot and standard release triptoreline in in vitro fertilization: pituitary sensitivity, luteal function, pregnancy outcome, and perinatal results

OBJECTIVE To compare the effects of depot and standard release form of triptoreline in superovulation induction in IVF programs. DESIGN One hundred ninety-six patients undergoing IVF were randomized between two treatment groups. Pituitary desensitization was obtained in group 1 (102 patients) with a single IM injection of 3.75 mg D-Trp-6-luteinizing hormone-releasing hormone (LH-RH) and, in group 2 (94 patients), with daily SC administration of 0.1 mg D-Trp-6-LH-RH. In a subgroup of 11 patients, a series of GnRH tests was performed to investigate pituitary desensitization and, in another subgroup of 12 patients, a study of luteal phase steroid profile was performed. In an additional 23 patients, a series of GnRH tests were performed to investigate pituitary desensitization during the late follicular and midluteal phases. RESULTS No differences were found in the time necessary to reach desensitization (11.3 +/- 1.03 versus 11.3 +/- 1.45 days; mean +/- SEM), whereas resumption of pituitary activity takes place in 7 days after the discontinuation of the daily form and in about 2 months after discontinuation of the depot form. No differences were found in the duration of stimulation, number of FSH ampules, E2 levels, and number of follicles (11.7 +/- 0.68, versus 12.2 +/- 0.68) on hCG administration day and the total oocytes collected (9.1 +/- 0.6 versus 9.2 +/- 0.64). Oocyte quality, percentage of fertilization and cleavage, pregnancy rate per transfer (28.7% versus 25.6%), and miscarriages (about 30%) were similar in the two protocols. No difference was found in hormonal levels during the luteal phase. In both groups there was a high incidence of multiple pregnancy. CONCLUSION Comparable results can be achieved with both long-acting and standard-release forms of GnRH analogs in patients undergoing assisted reproduction in terms of follicular stimulation and abortion rates despite differences in the duration of pituitary suppression.

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.

Comparison between depot leuprorelin and daily buserelin in IVF

ObjectivesTo compare the effects of depot and daily forms of GnRH analogs in IVF programs.MethodsOne hundred seventeen patients undergoing IVF, with no severe male factor, were randomized between two treatment groups. Pituitary desensitization was obtained in group 1 (60 patients) with a single IM injection of leuprorelin (3.75 mg), and in group 2 (57 patients) with buserelin (0.3 mg SC twice daily). In a subgroup of 10 patients (5 for the depot form and 5 for the daily form) several GnRH tests were performed to investigate pituitary desensitization.ResultsNo differences were found in the time to reach desensitization. Resumption of pituitary activity occurred in 7 days with the daily form and in about 2 months with the depot form. No significant differences were found in the stimulation pattern, oocyte quality, percentage of fertilization. The pregnancy rate per transfer was slightly, but not significantly, better in the depot group (29.4% vs 25.9%). Implantation rate (11.9% vs 12.3%) and the percentage of miscarriages (26.6% vs 28.5%) were similar.ConclusionDepot and daily forms of GnRH analogs are equally effective in superovulation induction for IVF. Considering improved patient compliance and preference, depot forms are advantageous.

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.

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.

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.

Births after transcervical gamete intrafallopian transfer with a falloposcopic delivery system

OBJECTIVE To evaluate the safety and efficiency of a new delivery system to perform transcervical GIFT. DESIGN Evaluation of pregnancy rate (PR), miscarriage rate, ectopic pregnancy rate, and delivery rate. SETTING Institute of Obstetrics and Gynecology, Reproductive Endocrinology Unit, Infertility and IVF Center. PATIENT(S) Twenty-five patients with patent tubes documented by laparoscopy plus falloposcopy. INTERVENTION(S) Superovulation was induced with GnRH analogue and FSH. Under laparoscopic control, transcervical cannulation of the tube was done using a linear everting catheter incorporating direct falloposcopic vision of the tubal lumen. Two lengths of everting catheter (3 and 6 cm) were used providing either isthmic-ampullary or midampullary placement of the inoculum. A comparison was done in terms of ease of access and transfer, falloposcopic observations, and PRs between the groups. MAIN OUTCOME MEASURE(S) Efficacy was established by evaluating the PR, miscarriage rate, ectopic pregnancy rate, and delivery rate. RESULT(S) The PR was 28% (with no differences between the lengths of everting catheters). No ectopic pregnancies occurred. The abortion rate was 28.6% and the delivery rate was 20%. Neither tubal perforation nor other complications occurred during the procedure. CONCLUSION(S) Falloposcopic GIFT is safe and efficient and may be a less invasive alternative than laparoscopic transfer.

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.