Monica Cattoli

Predictive factors for embryo implantation potential

In spite of recent improvements in IVF, pregnancy rates have not increased significantly and one of the major problems remains the high multiple pregnancy rate. Better criteria are therefore necessary to establish the viability of a transferable embryo. Early prognosis of the developmental fate of the oocyte would help in selecting the best embryos to transfer, but non-invasive selection at the oocyte stage (extracytoplasmic and intracytoplasmic morphology) has proved to be of little prognostic value. Recently, it has been shown that follicular vascularization appears to be predictive of oocyte developmental fate, making it a good first-step approach for selection. Observation of pronuclei patterns at the zygote stage appears to offer an additional prognostic tool, correlating well with IVF outcome. Morphological evaluation of the embryo at days 2-3 remains the most used and valid method of selection, even though it is not sufficient to select embryos with the higher implantation potential. Blastocyst culture is another possible strategy for selecting the best embryos with reduced risk of aneuploidies, though not all major chromosomal aberrations are excluded by prolonged in-vitro culture. In summary, selecting the best embryo for transfer is a decision that should be based on choices made during the different stages of assisted reproductive technologies.

Oocyte donation program: pregnancy and implantation rates in women of different ages sharing oocytes from single donor*

OBJECTIVE To investigate the importance of uterus age as regards of pregnancy, implantation, and abortion rates using the oocyte donation model. DESIGN Retrospective data analysis of cases where recipients of different ages shared oocytes from single donor. SETTING A tertiary infertility center. PATIENTS One hundred fourteen women (21 to 49 years of age) undergoing a total of 114 cycles of oocyte donation were divided into two groups according to age (group A < = or 39 years: group B between 40 and 49 years). INTERVENTIONS Hormonal replacement therapy was given using increasing doses of 17 beta-E2 (2, 4, and 6 or 8 mg) and either 100 mg of P in oil or 600 mg of micronized P through the vaginal route. MAIN OUTCOME MEASURES Pregnancy, abortion, and implantation rates. RESULTS Fifty-seven transfer cycles were performed per age group. Twenty-seven clinical pregnancies were achieved in Group A and 14 in group B, with pregnancy rates (PRs) of 47.3% and 24.5%, respectively. There were four abortions in group A and one in group B, resulting in abortion rates of 14.8% and 7%, respectively. Thirty-four of 137 transferred embryos in group A and 20 of 134 in group B implanted, resulting in implantation rates of 24.8% and 14.9%, respectively. CONCLUSION This study seems to suggest that there are differences in pregnancy and implantation rates in recipients of different ages because of uterine receptivity. Fertility therefore does not depend merely on oocyte age and quality but also on uterine age.

Evidence-based clinical outcome of oocyte slow cooling

In the last few years, there has been a significant improvement in oocyte cryopreservation techniques. To investigate the clinical significance of oocyte freezing, an assessment of the cumulative pregnancy rate per started cycle derived from the use of fresh and frozen-thawed oocytes was performed. Between 2004 and 2006, 749 cycles were carried out, in which no more than three fresh oocytes were inseminated either by standard IVF or microinjection. Supernumerary mature oocytes were cryopreserved by slow cooling. Cryopreservation of fresh embryos was performed in rare cases to prevent the risk of ovarian hyperstimulation syndrome using a standard embryo freezing protocol. Fresh embryo transfer cycles totalled 680, 257 of which resulted in pregnancy. The pregnancy rates per patient and per transfer were 34.3% and 37.8% respectively. When frozen-thawed oocytes were used, following 660 thawing cycles, 590 embryo transfers were performed in 510 patients. Eighty-eight pregnancies were achieved with embryos from frozen oocytes, with a success rate of 17.2% per cycle. When fresh and frozen-thawed cycles were combined, the number of pregnancies was 355, giving a cumulative pregnancy rate of 47.4%. Oocyte cryopreservation can contribute considerably to the overall clinical success, ensuring a cumulative rate approaching that achievable with embryo storage.

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.

Clinical Efficiency of Oocyte and Embryo Cryopreservation

The assessment of the standard for success of in vitro fertilization (IVF) treatment is an arduous task. Clinical efficiency and safety of a given procedure should represent fundamental tools for objective comparison. However, differences in patient populations, laboratory protocols, and expression of clinical data make the analysis of different studies and strategies very difficult. Formulation of the standard for success through the cumulative delivery rate per cycle of stimulation is a very attractive option because it includes the essential contribution of frozen embryos, which can represent 30–40% of all deliveries, while taking into account the need to minimize the proportion of pharmacological and surgical treatments. Embryo cryopreservation may be applied at different postinsemination stages. Larger and more detailed sets of data are available for day 2 embryo freezing, which allows cumulative delivery rates of 50–60% in good prognosis patients. In the last few years, novel freezing methods have improved the overall efficiency of oocyte cryopreservation. Especially in contexts afflicted by legal restrictions to embryo cryo‐ preservation, this form of preservation has started to have an impact on the IVF standard of success, generating cumulative pregnancy rates approaching 50%. Despite having been applied systematically by some IVF programs for only a few years, oocyte freezing already competes in efficiency with pronuclear‐stage cryopreservation, and it does not appear unrealistic to predict that in the future it will challenge the dominance of embryo cryopreservation as the preferred form of conservation.

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.

CLINICAL ASSISTED REPRODUCTION: Effect of Duration of Estradiol Replacement on the Outcome of Oocyte Donation

Purpose: To investigate if duration of estrogenic endometrial stimulation can affect recipient pregnancy rate in an ovum donation program.Methods: Each recipient received micronized 17 β-estradiol orally in a steadily increasing dosage from 2 to 6 mg daily over a period of time varying from 5 to 76 days until oocyte were available for donation. Recipients (520 patients for a total of 835 transfer cycles) were retrospectively divided into five groups depending on the duration of E2 administration.Results: No significant difference was seen in pregnancy and implantation rates between groups. There was a higher number of miscarriages in Group A (41%), p < 0.05 vs. Group B (15%), and vs. Group E (1%). Age, number of pregnancies and miscarriages, or implantation rate in donors (327 women aged <35 years) were similar in all the five groups.Conclusions: Endometrial receptivity is tolerant to a wide duration of E2 treatment (until 2 months), while waiting for oocytes available for donation, but best results are achieved with a treatment range of 11 to about 40 days.

Artificial Reproductive Technology Achievements for Optimizing Embryo Quality

Abstract: Evaluation of morphological characteristics, to date, has been the most widely accepted method for the selection of embryos with higher developmental ability and optimization of the outcome of in vitro fertilization (IVF). Improvement in clinical results has also been pursued through attempts to generate embryos of high quality or to identify more reliable selection criteria. This work evaluates the possibility of improving embryo quality and subsequent IVF outcome in situations in which creation of supernumerary embryos is not allowed. Optimization of gamete selection and conditions of insemination, such as hormonal therapy to improve sperm quality of patients undergoing intracytoplasmic sperm injection treatment, use of power Doppler image for follicle selection, short coincubation of gametes during insemination, and use of a polscope for spindle detection, is described.

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.