The Blastulation Rate Is Negatively Associated With Euploid Rate.

OBJECTIVES: To study the association between the blastulation rate, the presence of 1 pronucleus (1PN) zygotes, and the ploidy of the cohort of blastocysts. METHODS: A cross-sectional study using the existing databases of 2 university fertility centres in Canada. We included 345 cycles from 235 couples who underwent next-generation sequencing preimplantation genetic testing for the detection of aneuploidy in the study. RESULTS: A total of 1456 blastocysts were biopsied. In multivariate analysis, only female age and the number of 1PN/2PN embryos showed a negative association with euploid ratio. Surprisingly, when the analysis was limited to cycles with no delayed blastulation, the blastulation rate was also negatively associated with the euploid ratio. CONCLUSIONS: This study sheds some light on the stages of early embryo development. Further study on the mechanisms governing embryo development and the different cell cycle checkpoints in embryo development is warranted.

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.

Obstetric outcomes following vitrification of in vitro and in vivo matured oocytes.

OBJECTIVE: To evaluate obstetric outcomes with oocyte vitrification after ovarian stimulation (OS) and in vitro maturation (IVM) of immature oocytes. DESIGN: A prospective trial from October 2003 to April 2007. SETTING: University-based medical center. PATIENT(S): OS group: 38 patients undergoing intrauterine insemination who overresponded to OS. IVM group: 20 patients who had previous unsuccessful intrauterine insemination. INTERVENTION(S): Mature oocyte retrieval following OS. Immature oocyte retrieval and IVM. Oocyte vitrification, thawing, insemination, and transfer of the resulting embryos. MAIN OUTCOME MEASURE(S): Live-birth rates and obstetric outcomes. RESULT(S): The OS group was superior to the IVM group in terms of oocyte survival (81.4 +/- 22.6% vs. 67.5 +/- 26.1%), fertilization rate (75.6 +/- 22.5% vs. 64.2 +/- 19.9%), and cumulative embryo score (38.4 +/- 22.3 vs. 20.0 +/- 13.8). However, the differences in the implantation rate per embryo (19.1 +/- 25.8% vs. 9.6 +/- 24.1%), clinical pregnancy rate per cycle started (44.7%, vs. 20.0%), and live-birth rate per cycle started (39.5% vs. 20.0%) were not statistically significant. Twenty healthy babies were born in the OS group and four in the IVM group. CONCLUSION(S): Pregnancies achieved with vitrification of oocytes after OS and IVM treatments do not appear to be associated with adverse pregnancy outcomes. Vitrification of IVM oocytes represents a novel option for fertility preservation.

Live birth after vitrification of in vitro matured human oocytes.

OBJECTIVE: To report the first healthy live birth from immature oocytes retrieved in a natural menstrual cycle, followed by in vitro maturation (IVM) and cryopreservation of the oocytes by vitrification. DESIGN: Case report. SETTING: University-based tertiary medical center. PATIENT(S): A 27-year-old woman with tubal disease and polycystic ovaries. INTERVENTION(S): Immature oocytes were retrieved by transvaginal ultrasound guided follicle aspiration on day 13 of her natural menstrual cycle, matured in vitro and vitrified. The oocytes were thawed in a subsequent menstrual cycle, inseminated by intracytoplasmic sperm injection, and the resulting embryos transferred. MAIN OUTCOME MEASURE(S): Oocyte maturation and survival rates, pregnancy, and live birth. RESULT(S): One metaphase II and 18 germinal vesicle stage oocytes were collected; 16 out of 18 germinal vesicle oocytes matured, and a total of 17 oocytes were vitrified. After thawing, four IVM oocytes survived; three embryos were transferred. The woman went on to deliver a single healthy live baby at term. CONCLUSION(S): We provide proof-of-principle evidence that the novel fertility preservation strategy of immature oocyte retrieval, IVM, and vitrification of oocytes can lead to successful pregnancy and healthy live birth.

Pregnancy loss in pregnancies conceived after in vitro oocyte maturation, conventional in vitro fertilization, and intracytoplasmic sperm injection.

OBJECTIVE: To compare rates of pregnancy loss after oocyte maturation in vitro (IVM), after IVF, and after intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective comparative study. SETTING: University tertiary-care center for infertility. PATIENT(S): Women undergoing assisted reproductive technology in a single center. INTERVENTION(S): Oocyte maturation in vitro, IVF, or ICSI, as indicated. MAIN OUTCOME MEASURE(S): Biochemical pregnancy, clinical miscarriage, ectopic pregnancy, and late fetal loss. RESULT(S): There were 1,581 positive pregnancy tests (120 IVM, 849 IVF, and 612 ICSI). The biochemical pregnancy loss rate did not statistically significantly differ among the groups: 17.5% (21/120) after IVM, 17.0% (144/849) after IVF, and 18.0% (110/612) after ICSI. The clinical miscarriage rate after IVM was 25.3% (25/99), which was statistically significantly different compared with 15.7% (111/705) after IVF and 12.6% (63/502) after ICSI. However, the clinical miscarriage rates in women with polycystic ovary syndrome were statistically similar, at 24.5% (24/98) after IVM and 22.2% (18/81) after IVF. The ectopic pregnancy rates also were statistically similar: 1.0% (1/99) after IVM, 2.3% (16/705) after IVF, and 1.8% (9/502) after ICSI. The late fetal loss rates were similar as well: 1.0% (1/99) after IVM, 2.7% (19/705) after IVF, and 2.9% (14/502) after ICSI. There were no chromosomal abnormalities in the IVM group. CONCLUSION(S): There is a higher rate of clinical miscarriage after IVM when compared with IVF and ICSI. This appears to be related to polycystic ovary syndrome rather than to the IVM procedure.

Obstetric outcomes and congenital abnormalities after in vitro maturation, in vitro fertilization, and intracytoplasmic sperm injection.

OBJECTIVE: To compare obstetric outcome and congenital abnormalities in pregnancies conceived after in vitro maturation (IVM), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) with those in spontaneously conceived controls. METHODS: Data were collected from the McGill Obstetrics and Neonatal Database (MOND). All children were examined and classified in a standard manner. Final data were reviewed 12 months after delivery. Pregnancies by IVM, IVF, and ICSI were compared with those of age- and parity-matched controls. Congenital abnormality, gestational age, birth weight, Apgar scores, cord pH, growth restriction, pregnancy complications, mode of delivery, and multiple pregnancy were compared. RESULTS: A total of 432 children were born from 344 pregnancies after assisted reproductive technology (ART) during the study period (IVM 55, IVF 217, ICSI 160). The observed odds ratios (ORs) for any congenital abnormality were 1.42 (95% confidence interval [CI] 0.52-3.91) for IVM, 1.21 (95% CI 0.63-2.62) for IVF, and 1.69 (95% CI 0.88-3.26) for ICSI. Twin pregnancy (IVM 21%, IVF 20%, ICSI 17%) and triplet pregnancy (IVM 5%, IVF 3%, ICSI 3%) were higher than those in controls (1.7% twins and 0% triplets) (P<.001). Cesarean delivery rates were higher after ART, even in singleton pregnancies (IVM 39%, IVF 36%, ICSI 36%; controls: 26.3%) (P<.05). Apgar scores, cord pH, growth restriction, and pregnancy complications were comparable in all groups. CONCLUSION: All ART pregnancies are associated with an increased risk of multiple pregnancy, cesarean delivery, and congenital abnormality. Compared with IVF and ICSI, IVM is not associated with any additional risk.

Ultrasonography in polycystic ovary syndrome: an update.

Polycystic ovary syndrome (PCOS) is a convergence of multisystem endocrine derangements. During the last decade, the role of ultrasonography in the diagnosis and monitoring of this endocrinopathy underwent significant changes. However, there remain many concerns about whether these changes should be more widely introduced in clinical practice. Current concepts include the use of high-resolution, 3-dimensional ultrasound instead of conventional 2-dimensional ultrasound; formulaic methods of measuring ovarian volume; and correlation between ultrasonographic features, biochemical indices and ovarian stromal changes, such as enhanced echogenicity and increased blood flow. These issues, together with the new Rotterdam 2003 European Society of Human Reproduction and Embryology (ESHRE)/American Society for Reproductive Medicine (ASRM)-sponsored consensus criteria for the diagnosis of PCOS, are discussed in this review article.

Retrieval of immature oocytes followed by in vitro maturation and vitrification: a case report on a new strategy of fertility preservation in women with borderline ovarian malignancy.

BACKGROUND: We report a novel fertility preservation strategy in a woman with borderline ovarian tumors involving retrieval of immature oocytes, in vitro maturation (IVM) and subsequent cryopreservation. CASE: A 43-year-old woman underwent laparotomy for cystic ovarian masses on day 18 of her menstrual cycle. A diagnosis of bilateral borderline ovarian tumors was made following histological frozen section analysis. Left salpingo-oophorectomy, right ovarian cystectomy, omentectomy and lymph node sampling were performed. All visible follicles on the surface of the removed ovary were aspirated. Four immature oocytes were retrieved and underwent IVM. Three oocytes matured after 48 h and were cryopreserved. CONCLUSION: Immature oocytes can be successfully isolated from the oophorectomy specimen regardless of the day of menstrual cycle, matured in vitro and cryopreserved, providing a possible strategy for fertility preservation in this group of women.

A review and meta-analysis of prospective trials comparing different catheters used for embryo transfer.

OBJECTIVE: To determine the relative efficacy of different types of embryo transfer (ET) catheters. DESIGN: Systematic review and meta-analysis of prospective randomized, controlled trials comparing at least two different ET catheters. SETTING: Infertility centers providing treatment with in vitro fertilization/embryo transfer (IVF-ET). PATIENT(S): Women undergoing ET. INTERVENTION(S): Embryo transfer with soft or hard catheters. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): A total of seven prospective trials were identified that compared soft (Cook or Wallace) catheters with hard (TDT, Frydman, Tomcat, Rocket) catheters. The meta-analysis demonstrated an increased chance of clinical pregnancy when soft ET catheters were used. The TDT catheter was compared against both soft catheters and other hard catheters, showing decreased chance of clinical pregnancy when the TDT catheter was used. Six more prospective trials were identified comparing the Cook and Wallace soft catheters, and the meta-analysis of these data showed no demonstrable difference in clinical pregnancy rates. CONCLUSION(S): An increased chance of clinical pregnancy is achieved when soft ET catheters are used. There appears to be little difference between the Cook and Wallace soft catheters.

Congenital abnormalities in children born after assisted reproductive techniques: how much is associated with the presence of infertility and how much with its treatment?

Although there is increasing evidence to link couples with infertility undergoing all assisted reproductive technologies, particularly intracytoplasmic sperm injection (ICSI), and congenital abnormalities, the reasons remain unclear. Much evidence suggests that infertility itself might be a risk factor, and further long-term follow-up studies involving different possible control groups will help determine whether these abnormalities are directly related to treatment.

Natural-cycle in vitro fertilization combined with in vitro maturation of immature oocytes is a potential approach in infertility treatment.

OBJECTIVE: To describe pregnancies and live births that resulted from IVF of mature oocytes retrieved from dominant follicles in a natural cycle combined with in vitro maturation (IVM) of immature oocytes retrieved from small follicles. DESIGN: Case reports. SETTING: McGill Reproductive Center, Royal Victoria Hospital, McGill University. PATIENT(S): Three women with normal ovaries or polycystic ovaries who underwent infertility treatment. INTERVENTION(S): Administration of s.c. hCG (10,000 IU) 36 hours before oocyte retrieval in a natural cycle. After aspiration of all follicles, mature oocytes were inseminated immediately; immature oocytes were matured in vitro, inseminated by intracytoplasmic sperm injection (ICSI), and then the embryos transferred. MAIN OUTCOME MEASURE(S): Pregnancy and live birth. RESULT(S): Three pregnancies (two live births and one ongoing at time of writing) were achieved after the combination of natural-cycle IVF with IVM after transfer of the resulting embryos. CONCLUSION(S): Natural-cycle IVF combined with IVM might be a new approach to IVF treatment for women with various causes of infertility.

Randomized, controlled trial of priming with 10,000 IU versus 20,000 IU of human chorionic gonadotropin in women with polycystic ovary syndrome who are undergoing in vitro maturation.

Preretrieval priming with 10,000 IU hCG can improve oocyte maturation rates in vitro for women undergoing in vivo maturation treatment, though the optimum dose is unknown. This prospective, randomized, controlled trial demonstrated no improvement in oocyte maturation rates with 20,000 IU of hCG compared with 10,000 IU of hCG and therefore no benefit of the higher dose.

Human chorionic gonadotropin for in vitro oocyte maturation: does it improve the endometrium or implantation?

OBJECTIVE: To determine the effect of human chorionic gonadotropin (hCG) priming on endometrial receptivity in women with polycystic ovary syndrome undergoing in vitro maturation. STUDY DESIGN: The study was a randomized, controlled trial. After a withdrawal bleed, on day 8-10 of the cycle, women were randomized to receive 10,000 IU hCG or none 36 hours before immature oocyte retrieval. Oocytes were matured and fertilized, and up to 3 embryos were transferred. Prior to transfer, endometrial thickness, uterine artery pulsatility index and subendometrial bloodflow were determined. RESULTS: There was no difference in endometrial thickness (10.1 vs. 10.4 mm), uterine artery pulsatility index (2.45 vs. 2.65) or absent subendometrial bloodflow (23% vs. 18%) between the treatment and control groups. Higher numbers of embryos were produced in the treatment group (7.0 vs. 3.6), resulting in more pregnancies, although the implantation rates (16.7 vs. 16.0%) were similar. CONCLUSION: Preretrieval hCG priming does not improve the ultrasound parameters of endometrial receptivity or the implantation rate, although more embryos are generated.

In-vitro maturation of human oocytes.

Immature human oocytes can be matured and fertilized in vitro. However, subsequent embryonic development is different when the immature oocytes are retrieved in different situations. Exposure to the LH surge in vivo may be important for the oocytes to acquire the competence for maturation and subsequent embryonic development. The size of the follicles may also be an important feature for subsequent embryonic development. However, the developmental competence of oocytes derived from small antral follicles does not seem to be adversely affected by the presence of a dominant follicle. Oocyte maturation in vitro is profoundly affected by culture conditions. Gonadotrophins are required for oocyte maturation in vivo, but any requirement in vitro is still unclear. Recent clinical results from in-vitro matured (IVM) human oocytes are promising, although further research remains to be done in order to address the mechanisms of oocyte maturation and to improve culture conditions and also the implantation rate of embryos generated from IVM oocytes.

A meta-analysis of ultrasound-guided versus clinical touch embryo transfer.

OBJECTIVE: To determine the relative efficacy of ultrasound-guided embryo transfer and embryo transfer by clinical touch alone. DESIGN: Systematic review and meta-analysis of randomized, controlled trials comparing ultrasound-guided embryo transfer with embryo transfer by clinical touch alone. SETTING: Infertility centers providing treatment with in vitro fertilization/embryo transfer. PATIENT(S): Women undergoing embryo transfer. INTERVENTION(S): Embryo transfer with or without transabdominal ultrasound guidance. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and embryo implantation rate. RESULT(S): A total of eight prospective controlled trials were identified. Of these studies, four were nonrandomized or quasi-randomized and four were genuinely randomized. Meta-analysis demonstrated a significantly increased chance of clinical pregnancy following ultrasound-guided embryo transfer in all studies and in the genuinely randomized subgroup. The embryo implantation rate was also significantly increased following ultrasound-guided embryo transfer. CONCLUSION(S): Ultrasound-guided embryo transfer significantly increases the chance of clinical pregnancy and significantly increases the embryo implantation rate.

Predictive value of hypo-osmotic swelling test to identify viable non-motile sperm.

AIM: To determine the predictive value of the hypo-osmotic swelling (HOS) test to identify viable, non-motile sperm. METHODS: Semen samples from 20 men with severe asthenozoospermia underwent traditional seminal analysis, eosin-nigrosin (EN) staining and the HOS test. A further EN stain was then performed on a HOS pre-treated aliquot and a total of 2000 further sperm examined. RESULTS: The median sperm density was 5.1 million/mL (IQR 4.3 approximately 13.1) and the median motility was 3.0% (IQR 0 approximately 7). Seven samples showed complete asthenozoospermia. Initial EN staining showed 59% viability (range 48 approximately 69) despite the poor standard parameters and 47% (range 33 approximately 61) in the complete asthenozoospermia subgroup. The HOS test showed 49.9% reacted overall (range 40 approximately 59) and 41.7% (range 22 approximately 61) in the complete asthenozoospermia subgroup. The combined HOS/EN stain showed the positive predictive value of the HOS test to identify viable sperm was 84.2 % overall and 79.7% in the complete asthenozoospermia subgroup. CONCLUSION: The HOS test can effectively predict sperm viability in patients with severe and complete asthenozoospermia.

Effect of repeated assisted reproductive technology on ovarian response.

PURPOSE OF REVIEW: Based on current rates of success, many infertile couples who desire pregnancy have to undergo repeated cycles of assisted reproductive technology. Concern has been raised that repeated cycles of assisted reproductive technology may have a detrimental effect on future ovarian response and function, as well as pregnancy. This review summarizes current knowledge of the effects of repeated assisted reproductive technology, highlighting recent publications. RECENT FINDINGS: The available published evidence so far indicates that the follicular response and the number of oocytes retrieved appears to be maintained with repeated treatment and the only significant decline in ovarian response is because of an increase in female age. Similarly pregnancy and live birth rates decline to a small degree only up to cycle 3 or 4, with increasing female age again being the prime determinant. Encouraging patients to undertake repeated treatment without undue delay leads to improved cumulative rates of pregnancy and live birth. Current evidence does not indicate that ovarian stimulation leads to an increased risk of ovarian malignancy. SUMMARY: Couples should be counselled from the outset that assisted reproductive technology treatment is a continuum and a number of treatment cycles may be necessary. At present, there is little indication that repeated cycles have a detrimental effect on ovarian function, although the outcome of further research is awaited.

Consecutive transfer of day 3 embryos and of day 5-6 blastocysts increases overall pregnancy rates associated with blastocyst culture.

PURPOSE: To investigate whether the consecutive embryo transfer of day 3 embryos and of blastocyst protects against failure to reach embryo transfer and provides additional pregnancies. METHODS: An embryo transfer was performed on day 3 following which all remaining embryos were cultured to the blastocyst stage for a possible second transfer. RESULTS: One hundred and forty-two patients were selected for extended culture. Thirty-two of these patients did not develop blastocysts in culture, however, there were 12 pregnancies achieved in this group. CONCLUSIONS: The consecutive transfer of day 3 embryos and blastocysts can prevent the total loss of a cycle when embryos fail to develop to the blastocyst stage in culture and thereby provide additional pregnancies.