IVF Treatment Cycles Research Articles

Implantation Rate Remains Unaffected in Women with Endometriosis Compared to Tubal Factor Infertility

Purpose To reconsider the implantation and delivery rates which occurred six years later in women with endometriosis from the Yale IVF Programme. Methods Five hundred and ninety-seven consecutive IVF and ICSI treatment cycles were analyzed retrospectively. Patients with endometriosis (n=130; 258 cycles) were compared with an age-matched control group with tubal infertility (n=104; 206 cycles) and also with a group with male infertility (n=59; 133 cycles). Data from the endometriosis group were analyzed further in minimal-mild (144 cycles) and moderate-severe (114 cycles) subgroups. All the patients underwent laparoscopy prior to IVF treatment. Results Fewer oocytes were retrieved and similar fertilization (59% vs. 61%), implantation (12.3% vs. 16%), and delivery (23.7% vs. 26.3%) rates were found in patients with endometriosis compared to tubal infertility. A trend towards reduced pregnancy rate per transfer (17.5%) in the male infertility vs. endometriosis or tubal infertility groups (34% and 37.8% respectively) was observed. The number of embryos transferred in each group was comparable. Analysis of first cycles only across all groups revealed that the implantation rate did not have any statistically significant differences in the endometriosis versus the tubal or male infertility groups. Within the endometriosis group, the implantation, pregnancy, and delivery rates were similar in subgroups. Conclusions We conclude that in patients with endometriosis, implantation, pregnancy, and delivery rates are similar with tubal factor infertility, and higher compared to male infertility. Our results suggest that embryo quality and uterine receptivity remain unaffected in women with endometriosis.

WITHDRAWN: Human menopausal gonadotropin versus recombinant follicle stimulation hormone for ovarian stimulation in assisted reproductive cycles.

hMG and recombinant FSH, have both been used successfully for controlled ovarian hyperstimulation in in vitro fertilization and embryo transfer (IVF-ET). To compare the effectiveness of hMG with rFSH in ovarian stimulation protocols in IVF or ICSI treatment cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 3rd Jan 2002), PubMed, MEDLINE, Web of Science (all searched 1985 to May 15 2002), and reference lists of articles. We also contacted manufacturers and researchers in the field. Randomised trials comparing hMG with rFSH for ovarian stimulation in IVF or ICSI treatment for treatment of infertility in normogonadotrophic women. The main outcome measure was ongoing pregnancy/live birth per woman.Secondary outcomes included total gonadotrophin dose used, cancellation, number of oocytes retrieved, implantation, clinical pregnancy per woman, multiple pregnancy, spontaneous abortion and ovarian hyperstimulation syndrome. Peto odds ratios (OR) for hMG relative to rFSH were calculated after testing for homogeneity of treatment effect across all trials. Analyses were performed separately for the three different GnRHa protocols used: (1) without GnRHa down-regulation, (2) with GnRHa down-regulation using a short protocol and (3) with GnRHa down-regulation using a long protocol. Eight trials that met the inclusion criteria could be identified. One trial did not use down-regulation, one trial used a short protocol and six trials used a long down-regulation protocol. In the one trial with non-down-regulated women and in the one trial that used a short down-regulation protocol there was no evidence of a difference between hMG and rFSH in any clinical outcome. Data of four truly randomised trials in women down-regulated using a long protocol could be pooled. There was no evidence of a difference between hMG and rFSH in ongoing pregnancy/live birth per woman (OR 1.27; 95% CI 0.98 to 1.64). Furthermore there was no clear difference on any of the secondary outcomes, although the clinical pregnancy rate per woman was of borderline significance in favour of hMG (summary OR 1.28; 95% CI 1.00 to 1.64). The other secondary outcomes were comparable for both gonadotrophins. For all three GnRHa protocols analysed there is insufficient evidence of a difference between hMG and rFSH on ongoing pregnancy or live birth. More large randomised trials are needed to estimate the difference between hMG and rFSH more precisely. Such trials should preferably (1) use a consistent long GnRHa protocol and (2) use a fixed dose of gonadotrophin such to prevent potentially subjective decisions of the clinician in dosing and (3) take live birth as primary endpoint. At this moment in time however, in prescribing gonadotrophins for ovarian hyperstimulation in IVF one should use the least expensive medication.

Cross-validation and predictive value of near-infrared spectroscopy algorithms for day-5 blastocyst transfer

Near-infrared (NIR) spectroscopic metabolomic profiling of spent embryo-culture media has been used to calculate a viability score for individual embryos. These scores have been found to correlate to the reproductive potential of cleavage-stage embryos. In this study, 137 spent blastocyst media samples were collected after single-embryo transfer and analysed by NIR spectroscopy to generate an algorithm and calculate viability scores. To blindly validate the algorithm development process, another algorithm was trained on 47 preselected samples from clinic 1 and then used to predict the outcome of 42 samples from clinic 2. The overall pregnancy rate from the two clinical sites was 50.4%. A positive correlation ( R 2 = 0.82, P = 0.03) was observed with the increasing viability score quintiles and their associated implantation rates. Cross-validation of an algorithm generated from NIR analysis of media samples at one clinical setting blindly was shown to predict implantation potential of blastocysts cultured at another clinic in a different culture media and culture volume. This study demonstrates that metabolomic profiling by NIR spectroscopic analysis of day-5 spent embryo-culture media can predict the implantation potential of blastocysts. Furthermore, this method may not be restricted to a specific set of culturing conditions. The successes of IVF treatment cycles are in part limited by the ability to select the best single embryo from a cohort of patient embryos for transfer back to the woman. Routine procedures of embryo selection are based on morphology, including cell number and size, and the timing of cell division. These methods are favoured because they are quick and easy to assess. Human embryos are grown in culture solutions, which are specific for their stage of development. Recent studies analysing the culture solution in which the embryo are grown, by near infrared (NIR) spectroscopic analysis, have been able to predict if an embryo will implant or not. As culture conditions often vary between IVF laboratories the questions remained if the NIR technique could be used to independently predict the implantation potential of an embryo cultured at one laboratory using an algorithm trained on embryos at a second clinic, a so-called cross-validation. The results of this study show that NIR spectroscopy can predict the ability of embryos to implant even when grown in different IVF laboratories and in two different culture solutions. This information supports the idea that NIR spectroscopy can be used globally not relying on specific culture conditions or media.

Elective single blastocyst transfer and the cryo-augmentation effect of aseptic vitrification: a comparison of two strategies

OBJECTIVE: In IVF treatment cycles, the number of good quality embryos on day 3 often weighs into the decision whether or not to proceed towards blastocyst transfer. This study compares the outcome of two embryo transfer policies: (1) single blastocyst transfer irrespective of day 3 embryo evaluation versus (2) single blastocyst transfer only if at least 4 good quality embryos are available on day 3. DESIGN: A retrospective review of 590 IVF cycles with patients grouped based on whether a day 5 transfer was planned (n=341) or day 5 transfer depended on a day 3 evaluation (n=249). MATERIALS AND METHODS: Blastocyst vitrification was performed with the closed CBS high security straws. No differences were observed in the age, rank of trial, days of stimulation and total gonadotropin dose. Neither was there a difference observed in total number of cumulus-oocyte complexes, MII oocytes or 2PN oocytes. RESULTS: Patients in the planned day 5 group have a lower subjects' fresh transfer rate (90.62 vs. 95.18% p<0.05) but no difference was seen in the fresh live birth and multiple pregnancy rates per initiated cycle (32.84 vs. 28.92%; 1.17 vs. 0%). Warmed blastocyst cycles of the planned day 5 group resulted in a similar transferable survival rate as blastocysts in the day 3 or day 5 group (69.9 vs. 76.5%). For thawing cycles, SET was equally performed in both strategies (87 vs. 78.05%). The projected cumulative ongoing pregnancy rate compensating for double counting in case subjects have more than one pregnancy is not different (42.58% vs. 39.84%). CONCLUSION: Elective day 5 transfer and aseptic vitrification offers an excellent ongoing pregnancy rate of 42.58%. Despite better fresh transfer rates, a transfer policy based on day 3 embryo evaluation does not affect the cumulative pregnancy rate.

Embryo development and pregnancy outcome of sibling pronuclear stage frozen and fresh human embryos

OBJECTIVE: Embryo cryopreservation has several potential advantages in IVF treatment cycles such as reducing the risk of multiple pregnancies, increasing the delivery rate per retrieval, and reducing the cost of treatment. The aim of this study was to compare the developmental potential of pronuclear stage (2PN) fresh and frozen sibling embryos.

The legal status of in vitro embryos

Judicial approaches to stored (cryopreserved) human embryos, in western jurisprudence, tend not to reflect approaches within systems of moral ordering or particular religious traditions, which differ among themselves. The emerging judicial approach is pragmatic, protecting individuals’ rights of control and their interests in parenthood. Embryos are approached instrumentally, not by reference to any inherent characteristics that may be attributed to them outside the law. Political legislatures may adopt religious approaches, such as by prohibiting embryo preservation and limiting how many may be created in an IVF treatment cycle. Legislatures may alternatively set time limits on embryo preservation, however, on expiry of which they must be left to natural degeneration. In treating human embryos as property, courts recognize owners’ powers of voluntary disposition, for instance by gift, but have held back from making financial assessments of their value, for instance on loss, consistently with legislation prohibiting their exchange for payment.

Gonadotropin-releasing hormone agonists versus antagonists for controlled ovarian hyperstimulation in oocyte donors: a systematic review and meta-analysis

To compare GnRH agonists and antagonists in oocyte-donation IVF treatment cycles by a systematic review and meta-analysis of trials. Systematic review and meta-analysis of randomized clinical trials (RCT). Systematic literature searches were conducted, and all randomized trials that compared GnRH agonists with antagonists in oocyte-donation IVF treatment cycles were included. Study selection, quality appraisal, and data extractions were performed independently and in duplicate. Tertiary fertility center. A total of 1,024 oocyte donors treated in eight RCTs. Comparison of GnRH agonists versus antagonists in oocyte-donation IVF treatment. Ongoing pregnancy, oocytes retrieved, duration of stimulation, gonadotropin consumption, and ovarian hyperstimulation syndrome incidence (OHSS) per randomized oocyte donor. Meta-analysis of these studies showed no significant difference in ongoing pregnancy rate between the GnRH agonists and antagonists (risk ratio [RR] 1.15, 95% confidence interval [CI] 0.97 to 1.36). The duration of stimulation was significantly lower with the GnRH antagonist protocol (weighed mean difference [WMD] -0.90 days, 95% CI -1.61 to -0.20). No significant differences were observed in the number of oocytes retrieved (WMD -0.60, 95% CI -2.26 to +1.07), gonadotropin consumption (WMD -264 IU, 95% CI -682 to +154), or OHSS incidence (RR 0.62, 95% CI 0.18 to 2.15). No significant differences were observed in ongoing pregnancy rate or the number of retrieved oocytes after donor stimulation with GnRH agonist or antagonist protocols.

Chromosome abnormality rates in human embryos obtained from in-vitro maturation and IVF treatment cycles

The aim of this retrospective study was to compare the incidence of chromosomal abnormality in embryos from in-vitro maturation (IVM) and IVF cycles. The copy numbers of chromosomes 13, 15, 16, 18, 21, 22, X and Y were assessed with fluorescence in-situ hybridization (FISH) in single blastomeres biopsied from cleavage stage embryos. Spare embryos that were not transferred or cryopreserved were also analysed in full. IVM and IVF groups comprised six and 30 couples, with mean ± SD embryos with FISH result of 8.0 ± 4.4 and 11.7 ± 3.8, respectively. The incidence of chromosomal abnormality per FISH result was similar in IVM and IVF embryos (58.7% versus 57.4%, respectively). When embryos were categorized based on maturation time of oocytes in IVM cycles, embryos derived from oocytes that matured 48 h after collection had a higher chromosomal abnormality rate compared with embryos derived from in-vivo matured oocytes and to embryos derived from oocytes that matured in the first 24 h after collection.

Who is at risk of emotional problems and how do you know? Screening of women going for IVF treatment

Fertility problems are accompanied by a lot of emotional distress, resulting in a considerable proportion of female patients showing severe maladjustment after assisted reproductive technology. Although this interferes with their daily life, emotional distress has also shown to be related to dropout of treatment and deterioration of health behaviour. Early identification of women at risk enables the provision of timely psychosocial support and the focusing psychosocial resources on those who need it most. This study investigated the psychometric characteristics of a screening tool SCREENIVF to identify women at risk of emotional problems at an early stage of treatment. Risk factors for emotional maladjustment were identified in a previous study and incorporated in SCREENIVF which consists of 34 items on general and infertility specific psychological factors. A group of 279 women in their first IVF treatment cycle completed SCREENIVF at both pretreatment and 3-4 weeks after the pregnancy test. Linear Regression analyses were performed to investigate the predictive value of SCREENIVF, and sensitivity and specificity as well as likelihood ratios were described. SCREENIVF successfully identified 75% of the patients as at risk or not at risk. The negative predictive value was high: 89%. The positive predictive value was low (48% in the total sample and 56% after unsuccessful treatment). Sensitivity was 69%, specificity was 77%. For its use as a first screening for emotional problems, SCREENIVF is an acceptable instrument to identify women at risk. These women could be offered more detailed diagnostics e.g. an interview to further investigate to what extent they could benefit from psychological treatment. In addition, physicians can anticipate on this risk profile when communicating with these patients.

Poor prognosis in cycles following “genuine” empty follicle syndrome

Objectives The aim of this study was to investigate the prognosis in future IVF cycles of patients with empty follicle syndrome (EFS). Study design EFS cases and their future cycles were reviewed. Clinical pregnancy rate per started cycle was taken as the primary outcome in assessing the future outcome in IVF treatment cycles. Results A total of 3023 patients underwent 5238 IVF treatment cycles. Twenty-six patients (1%) had a total of 58 (1%) cycles of EFS. Thirteen women went through 32 further IVF treatment cycles following the diagnosis of EFS, yielding only two clinical pregnancies, giving a clinical pregnancy rate of 6.25% per started cycle. In addition, four patients had recurrence in a total of 15 cycles. Conclusions The occurrence of EFS will indicate poor IVF success in subsequent IVF cycles. Patients with “genuine EFS” should be counselled about the outcome of their future IVF cycles.

THE CONTRIBUTIONS OF EMPIRICAL EVIDENCE TO SOCIO-ETHICAL DEBATES ON FRESH EMBRYO DONATION FOR HUMAN EMBRYONIC STEM CELL RESEARCH

This article is a response to McLeod and Baylis (2007) who speculate on the dangers of requesting fresh ‘spare’ embryos from IVF patients for human embryonic stem cell (hESC) research, particularly when those embryos are good enough to be transferred back to the woman. They argue that these embryos should be frozen instead. We explore what is meant by ‘spare’ embryos. We then provide empirical evidence, from a study of embryo donation and of embryo donors' views, to substantiate some of their speculations about the problems associated with requesting fresh embryos. However, we also question whether such problems are resolved by embryo freezing, since further empirical evidence suggests that this raises other social and ethical problems for patients. There is little evidence that the request for embryos for research, in itself, causes patients distress. We suggest, however, that no requests for fresh embryos should be made in the first cycle of IVF treatment. Deferring the request to a later cycle ensures that potential donors are better informed (by experience and reflection) about the possible destinations of their embryos and about the definition of ‘spare embryos’. Both this article, and that by McLeod and Baylis, emphasize the need to consider the views and experiences of embryo donors when evaluating the ethics of embryo donation for hESC research.

346 ULTRASTRUCTURE OF A HUMAN GIANT MII OOCYTE: CASE REPORT

The occurrence of giant oocytes has been reported with considerable frequency during IVF procedures in women of all ages and was associated with an increased response to gonadotrophin therapy. Previous studies suggested that giant oocytes, larger in diameter than normal oocytes and either at the GV, MI, or MII stage, might be a source of human digynic triploidy. However, to our knowledge there are no previous reports concerning the ultrastructure of human giant oocytes, and therefore the objective of this study was to characterize a human giant mature metaphase II oocyte from the ultrastuctural point of view. A giant oocyte with a visible polar body was used under informed consent, after controlled superovulation during a IVF treatment cycle. The oocyte was fixed with Karnovsky’s fixative, post-fixed in 2% OsO4 in 0.15 M cacodylate buffer, pH 7.2, dehydrated and embedded in Epon Semithin and ultrathin sections were cut with a diamond Diatome knife (Diatome, Hatfield, PA, USA) in a LKB ultramicrotome. Semithin sections were stained with aqueous azur II and methylene blue (1:1). Ultrathin sections were collected on 200 mesh copper grids (Taab Laboratories Equipment Ltd, Aldermaston, UK) and stained with 3% aqueous uranyl acetate (20 min) and Reynolds lead citrate (10 min). Contrast ultrathin sections were observed in a JEOL 100XII transmission electron microscope (JEOL Ltd., Tokyo, Japan) operated at 60 Kv. Cytogenetic analysis was not performed in this oocyte. At the time of collection, the giant oocyte was 1.4-fold larger than average size oocytes and contained a fragmented polar body. The zona pellucida had a normal loosely fibrillar structure and the perivitelline space was normal containing remnants of follicular cells. The cytoplasmic organelles were no uniformly dispersed with a large organelle-free zone (lake) observed in the periphery of the oocyte cortex and smaller focal lakes visible in the subcortex. Within the cortex the dense cortical vesicles were reduced in number and did not form one or two continuous rows beneath the oolemma. Smooth endoplasmic reticulum (SER) aggregates of tubules were also scarce but underdeveloped SER aggregates of tubules were present in the cortex. The distribution of the SER large and middle vesicles was abnormal: these organelles were nearly absent in the cortex but present in the inner cytoplasm. The content of some vesicles was denser than normal. We also observed the presence of several large secondary lysosomes filled with multiple small and medium lipid droplets (lipofuscin bodies), corresponding to retractile bodies located in the cortex. Large dense vesicles of different densities and volumes were found in the cortex and subcortex. The polar body showed very few cortical vesicles and did not contain mitochondria and SER large or small vesicles. The condensed chromosomes were aligned on the metaphase II plate, in the cortex of the oocyte. The ultrastructural alterations observed in this oocyte corroborated the conclusions of previous genetic studies and confirmed that giant oocytes are immature cytoplasmatically and would be associated with a higher frequency of abnormal development following fertilization. Thus, giant oocytes should not be used in IVF treatments. ASL was supported by FCT, Portugal.

Clinical application of comprehensive chromosomal screening at the blastocyst stage

To evaluate a new strategy for comprehensive chromosome screening at the blastocyst stage. Clinical research study. An IVF clinic and a specialist preimplantation genetic diagnosis laboratory. Forty-five infertile couples participated in the study. The mean maternal age was 37.7 years, and most couples had at least one previous unsuccessful IVF treatment cycle (mean 2.4). This study used a novel chromosome screening approach, combining biopsy of several trophectoderm cells on day 5 after fertilization and detailed analysis of all 24 types of chromosome using comparative genomic hybridization. Proportion of embryos yielding a diagnostic result, aneuploidy rate, implantation rate, and pregnancy rate. A diagnosis was obtained from 93.7% of embryos tested. The aneuploidy rate was 51.3%. The probability of an individual transferred embryo forming a pregnancy reaching the third trimester/birth was 68.9%, an implantation rate 50% higher than contemporary cycles from the same clinic. The pregnancy rate was 82.2%. The comprehensive chromosome screening method described overcomes many of the problems that limited earlier aneuploidy screening techniques and may finally allow preimplantation genetic screening to achieve the benefits predicted by theory. The high embryo implantation rate achieved is particularly encouraging and, if confirmed in subsequent studies, will be of great significance for IVF clinics attempting to reduce the number of embryos transferred or to implement single embryo transfer.

Ultrastructure and molecular cytogenetics of human metaphase II oocytes with granular vacuoles

AbstractStudies demonstrated poor fertilization rates and compromised early embryo development in cases of oocytes with dark and granular ooplasm, or with central granular ooplasm and presence of a refractile body. Many other structural abnormalities of human mature oocytes do exist, but remain to be evaluated. In the present study we characterized granular vacuoles (GVa) of mature metaphase II human oocytes. Surplus abnormal MII oocytes (n=6) with GVa were used under informed consent, after controlled superovulation during IVF treatment cycles. In all cases, patients had normal karyotypes. For electron microscopy oocytes were fixed with karnovsky fixative for 2h at 4°C, post-fixed in 1-2% OsO4 in buffer containing 0,8% K3Fe3+(CN)6, dehydrated in ethanol series, equilibrated with propylene oxide and embedded in Epon. Semithin sections were stained with aqueous azur II and methylene blue (1:1). Ultrathin sections were stained with 3% aquous uranyl acetate (20 min) and Reynols lead citrate (10 min). Sections were observed with a transmission electron microscope JEOL 100CXII operated at 60kV.

Hepatitis B infection and outcomes of in vitro fertilization and embryo transfer treatment

To examine the prevalence of hepatitis B virus (HBV) infection, the associated causes of subfertility, and the outcomes of the first IVF and embryo transfer treatment cycles in these infertile couples. A retrospective cohort study. Assisted reproduction technology (ART) unit. Two hundred eighty-seven couples undergoing IVF and embryo transfer cycles. Analysis of data on patients' characteristics, controlled ovarian hyperstimulation (COH), embryology, and pregnancy (PR) and implantation rates of IVF and embryo transfer cycles according to HBV serostatus of the infertile couples, which was routinely screened. The PRs and the implantation rates. Twenty-nine (10.1%) women were HBV seropositive, whereas 32 (11.1%) of their husbands were HBV seropositive. Concerning the causes of infertility, there was a trend toward more tubal blockage (57.1% vs. 42.2%) in the HBV-infected group. Among the 190 women undergoing their first IVF and embryo transfer cycles, both the ongoing PR or live birth rate and implantation rate in HBV group were significantly higher than the controls (53.3% vs. 24.2% per cycle with embryo transfer; and 43.3% vs. 18.4%, respectively). Our results demonstrate for the first time significantly higher PRs and implantation rates of IVF and embryo transfer cycles for couples with at least one partner being HBV seropositive. Further studies to elucidate the underlying mechanisms are warranted.

Report on the donation of supernumerary embryos from fresh IVF and ICSI treatment cycles for human stem cell research

Background.Research involving human embryos promises exciting therapeutic advances but raises ethical and moral dilemmas for scientists and potential donors. The aim of this study is to report the proportion of couples donating supernumerary fresh embryos for development of stem cell lines from a single centre and the characteristics of those who donate.Methods. Couples undergoing assisted conception treatment in a teaching hospital received research information between January 2005 and July 2006. Counselling and consenting was performed by a dedicated research nurse. Demographic data was collected for couples who enrolled in the study.Main outcome measures. To determine the proportion of couples willing to donate surplus embryos for stem cell derivation and to examine the characteristics of those who consent to donate.Results. Of 508 couples, 353 (69%) expressed an interest in research on their treatment consent forms. Sixty-six percent of those interested in research and 87% of counselled couples consented to donation. The demographic characteristics of those who agreed to donate were similar to those of all couples attending the unit.Conclusions. Approximately half of couples consented to donate under the described system in our centre. Detailed information provision helps the majority of those counselled to proceed to donation.

Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial

Studies in macaques have indicated that androgens have some synergistic effects with FSH on folliculogenesis. This study investigated the usefulness of pretreatment with transdermal testosterone in low-responder IVF patients. Randomized clinical trial including 62 infertile women who had a background of the first IVF treatment cycle cancelled because of poor follicular response. Patients were randomized in two treatment groups in their second IVF attempt. In patients in Group 1 (n = 31), transdermal application of testosterone preceding standard gonadotrophin ovarian stimulation under pituitary suppression was used. In Group 2 (n = 31 patients), ovarian stimulation was carried out with high-dose gonadotrophin in association with a minidose GnRH agonist protocol. The primary end-point was the incidence of low-responder patients. The main secondary outcome was the incidence of patients reaching ovum retrieval. The percentage of cycles with low response was significantly lower in Group 1 than in Group 2 (32.2 versus 71% 95% confidence interval for the difference, 15.7-61.6; P < 0.05). The number of patients with ovum retrieval tended to be higher in Group 1 than in Group 2 (80.6 versus 58.1% P = 0.09), the difference reaching statistical significance (81.2 versus 41.1%; P < 0.05) when only patients having normal basal FSH levels (16 and 17 patients in Groups 1 and 2, respectively) were considered. Pretreatment with transdermal testosterone may improve the ovarian sensitivity to FSH and follicular response to gonadotrophin treatment in previous low-responder IVF patients. This approach leads to an increased follicular response compared with a high-dose gonadotrophin and minidose GnRH agonist protocol.

Pregnancy and perinatal outcomes of infants born following in vitro maturation treatment

OBJECTIVE: The aim of this study was to compare pregnancy and perinatal outcomes of the infants born after in vitro maturation (IVM) treatment in order to evaluate the safety issue of IVM treatment. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Obstetric and perinatal data were collected from all pregnancies after IVM treatment from January 2003 to December 2007. A total of 42 pregnancies and 30 live births with 34 infants were analyzed. Multi-pregnancy, ectopic pregnancy, and miscarriage rates were compared with the outcomes of the same period from the conventional IVF treatment and ICSI treatment cycles. Gestational age, cesarean delivery rates, birth weight, Apgar scores, neonatal and obstertric outcome, congenital abnormalities of the all infants were also compared. RESULTS: There were no differences in multi-pregnancy, ectopic pregnancy, and miscarriage rates in IVM treatment compared with conventional IVF and ICSI treatment groups. Gestational age, cesarean delivery rates, birth weight, Apgar scores, neonatal and obstertric outcome, congenital abnormalities were comparable in IVM treatment with conventional IVF and ICSI treatment. CONCLUSIONS: Present study indicates IVM treatment does not increase multi-pregnancy, ectopic pregnancy and miscarriage rates. Also IVM treatment is not associated with any additional obstetric and perinatal risks.

Clinical and endocrine response to the withdrawal of gonadotropin-releasing hormone agonists during prolonged coasting

To compare the clinical and endocrine response of cycles in which GnRH agonists (GnRH-a) were stopped with cycles in which the agonists were continued during coasting. Retrospective study of stimulation cycles using flare and luteal agonist protocols. Academic. Fifty-nine IVF and intracytoplasmic sperm injection (ICSI) treatment cycles in 57 women, coasted for 3 or more days. The GnRH-a were withdrawn when E(2) levels continued to increase during coasting. Hormone concentrations, ultrasound findings, cycle cancellation, ovarian hyperstimulation syndrome (OHSS), oocyte retrieval, fertilization, embryo transfer, and clinical pregnancy rates (PR). In the GnRH-a withdrawn group E(2) levels decreased by 63% (18,043-6,656 pmol/L) without cycle cancellations or cases of severe OHSS. In the agonist continuation group, the spontaneous E(2) decrease was 29% (14,205-10,132 pmol/L) with cycle cancellation and severe OHSS rates of 9.5% (4/42) and 4.8% (2/42), respectively. Oocyte retrieval, fertilization, embryo transfer, and clinical PRs were not compromised by stopping the agonists. Variations in the dynamic responses of FSH, LH, anti-Müllerian hormone, P, and androstenedione (A) levels in these cycles are described. Withdrawal of GnRH-a during coasting interrupted increasing E(2) levels, prevented cycle cancellation, and mitigated the risk of OHSS in this high risk group without compromising oocyte retrieval, fertilization, embryo transfer, or PRs.

Ovarian stimulation for IVF has no quantitative association with birthweight: a registry study

Singleton children born after IVF are of lower birthweight compared with their naturally conceived peers. It has been hypothesized that ovarian stimulation might be associated with low birthweight in children born after IVF. The aim of the present study was to explore whether or not a dose relationship exists between ovarian stimulation and birthweight in singletons born after ovarian stimulation for IVF. Using a national IVF registry database with a coverage of 65-70%, parental demographic variables, treatment cycle variables and neonatal variables were retrieved from all IVF treatment cycles in women between 25 and 35 years of age in which gonadotrophins were used for ovarian stimulation and a fresh embryo transfer resulting in singleton live birth was performed. Birthweight was standardized as a z-score, adjusting for gestational week at delivery and fetal sex, using data from a large reference population. Multivariate regression analysis was used to investigate the association between the dependent variable z-score and the independent predictor variables maternal age (years), maternal weight (kg), maternal height (cm), maternal body mass index (BMI) (kg/m(2)), duration of infertility (years), number of embryos transferred (n), duration of stimulation (days), consumption of gonadotrophins (ampoules) and number of oocytes retrieved (n). Data retrieval yielded 32,416 singleton live births after IVF, with a mean (+/-SD) z-score of -0.25 (+/-1.0) and -0.23 (+/-1.0) for male and female neonates, respectively. Regression analysis indicated that maternal weight, maternal height, duration of infertility and the number of embryos transferred were statistically significant determinants of the birthweight of singletons after ovarian stimulation IVF. Parameters of ovarian stimulation (duration of stimulation, consumption of gonadotrophins, number of oocytes retrieved), maternal BMI and maternal age did not significantly predict birthweight. Features reflecting ovarian stimulation do not correlate with birthweight. Therefore, ovarian stimulation is unlikely to be a factor affecting birthweight of IVF pregnancies.