The first case described: monozygotic twin sisters with the fragile X premutation but with a different phenotype for premature ovarian failure.

OBJECTIVE: To describe the first case of monozygotic twin sisters with fragile X premutation and discordance for premature ovarian failure (POF). DESIGN: A descriptive case study. SETTING: Academic center. PATIENT(S): Monozygotic twin sisters with fragile X premutation and discordance for POF. INTERVENTION(S): Serum laboratory testing, fragile X premutation screening, zygosity testing, X-inactivation ratio and Southern blot studies. MAIN OUTCOME MEASURE(S): Incidence of POF in this twin cohort. RESULT(S): Zygosity analysis using polymerase chain reaction of 15 polymorphic markers via capillary gel electrophoresis in these patients confirmed their monozygosity. X-inactivation studies were performed using the human androgen receptor (HUMARA) gene and revealed similar X-inactivation ratios for both the patient and her sister (11:89 and 12:88, respectively) from peripheral serum samples. Southern blot evaluation of the proband and her sister revealed a similar methylation pattern in which the premutation allele was unmethylated much more than the normal allele. The contribution of the premutation on the active allele as determined by Southern blot analysis was consistent between sisters. CONCLUSION(S): The inactivation ratio studies and subsequent Southern blot analysis do not show differences between the patients; therefore, we are unable to identify a causative mechanism for the identical sisters' discordant phenotypes. It is possible that the inactivation ratios observed from the peripheral blood specimens obtained from the sisters do not represent the allele expression and skewing present at the level of the ovary.

In vitro fertilization outcomes in patients experiencing a premature rise in luteinizing hormone during a gonadotropin-releasing hormone antagonist cycle.

Patients undergoing controlled ovarian hyperstimulation and pituitary suppression with a GnRH antagonist who experienced a transient premature rise in LH were compared with those who did not have an early surge. Those experiencing a premature LH surge had equivalent clinical and ongoing pregnancy rates per ET.

A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups.

Gonadotropin-releasing hormone agonist to induce final oocyte maturation prevents the development of ovarian hyperstimulation syndrome in high-risk patients and leads to improved clinical outcomes compared with coasting.

Ninety-four women undergoing IVF with peak E2 level>4000 pg/mL received leuprolide acetate (LA) trigger (LA trigger group) or had gonadotropins withheld for one or more days (coasting group) followed by hCG trigger, unless cycle cancellation occurred. There were no cases of ovarian hyperstimulation syndrome in either group, and the LA trigger group had significantly more oocytes retrieved (26.9+/-9.5 vs. 17.7+/-9.3) P<0.001, more normally fertilized oocytes (15.0+/-7.8 vs. 10.3+/-6.3) P=0.01, and higher clinical and ongoing pregnancy rates than the coasting group (52.5% vs. 27.2%; 49.2% vs. 24.2%, P=0.02 for both comparisons, respectively).

Transfer of two versus three embryos in women less than 40 years old undergoing frozen transfer cycles.

OBJECTIVE: To compare outcomes of frozen embryo transfer (FET) cycles when two or three embryos were transferred in women aged <40 years. DESIGN: Retrospective chart review. SETTING: A university-affiliated IVF program. PATIENT(S): Women undergoing FET cycles between January 2004 and December 2005. INTERVENTION(S): Transfer of two or three embryos. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR), multiple pregnancy rate (MPR), and live birth rate (LBR). RESULT(S): In patients aged <35 (n = 145), two versus three embryo group had similar PR and LBR, but the MPR was significantly higher in the three-embryo group (41% for three embryos vs. 9.4% for two embryos). Clinical pregnancy in the fresh cycle from which the frozen embryos were obtained did not affect the PR, and an increase in MPR was still observed. In patients aged 35 to 39 (n = 93), there were no differences in the PR, MPR, or LBR between the two groups. CONCLUSION(S): Transfer of two instead of three frozen embryos in patients <35 years old resulted in a significant decrease in MPR without compromising PR or LBR. Transferring additional embryos when a patient had an unsuccessful fresh cycle was not warranted. In the age group 35-39 years, transferring two instead of three embryos did not decrease PR or LBR, and had no effect on the risk of high-order multiples.

Influence of embryo quality and number of previous cycles on pregnancy and multiple pregnancy rates in women aged 35 to 37 years who received two or three embryos.

Women aged 35-37 years undergoing IVF-ET with fresh embryos at a university infertility center were analyzed to evaluate factors useful in determining whether two or three embryos should be transferred in this age group. Embryo quality and number, but not number of previous failed cycles, were important in determining outcome, and all triplet pregnancies could have been avoided at our program in this age group by limiting the transfer to two good-quality embryos, without reducing pregnancy rates.

A randomized prospective study of microdose leuprolide versus ganirelix in in vitro fertilization cycles for poor responders.

Forty-eight patients who met the criteria of poor response during prior gonadotropin stimulation were enrolled in a randomized prospective study comparing a gonadotropin-releasing hormone (GnRH) antagonist protocol, using ganirelix acetate, with a microdose GnRH agonist protocol for in vitro fertilization-embryo transfer (IVF-ET). This pilot study contributes to the literature of poor response IVF treatment protocols because the use of ganirelix appears to be as effective as the microdose protocol and may be a superior choice in terms of cost and convenience for the patient.

Reducing the dose of human chorionic gonadotropin in high responders does not affect the outcomes of in vitro fertilization.

OBJECTIVE: The lowest effective hCG dose in high responders during IVF-embryo transfer (ET) has not been established. This study was performed to confirm that a dose of 3,300 IU is sufficient to provide adequate oocyte maturation and fertilization. DESIGN: Retrospective review of IVF clinical data. SETTING: Infertility center at a tertiary care university. PATIENT(S): Ninety-four IVF cycles were analyzed from high responders based on peak E(2) levels. Demographics were compared including age, diagnosis, and stimulation protocol. INTERVENTION(S): On the day of hCG administration, if E(2) levels were >/=2,500 but <4,000 pg/mL, patients received 5,000 IU (group A). For levels between 4,000 pg/mL and 5,500 IU pg/mL, they received 3,300 IU (group B). MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, proportion of mature oocytes, fertilization rates, chemical and clinical pregnancy rates (PR). The incidence and severity of ovarian hyperstimulation syndrome (OHSS) was also analyzed. RESULT(S): Mean ages were 35.4 +/- 0.7 and 33.2 +/- 0.7 for groups A and B, respectively. Peak E(2) levels differed significantly (2,907 +/- 76 vs. 4,260 +/- 129 pg/mL), as well as the mean number of eggs retrieved (15.9 +/- 0.9 vs. 20.3 +/- 1.2). Proportion of mature eggs (81.6% vs. 81.9%), fertilization rate (70.5% vs. 68.7%), chemical PR (58.7% vs. 58.7%), and clinical PR (50.0% vs. 43.5%) were similar. There was no difference in the incidence of mild, moderate, or severe OHSS. CONCLUSION(S): A reduced hCG dose of 3,300 IU results in a similar proportion of mature eggs, similar fertilization rates, and similar PRs compared to 5,000 IU. Reducing the dose of hCG does not eliminate the risk of OHSS in a high-risk group.

Freeze-dried sperm fertilization leads to full-term development in rabbits.

To date, the laboratory mouse is the only mammal in which freeze-dried spermatozoa have been shown to support full-term development after microinjection into oocytes. Because spermatozoa in mice, unlike in most other mammals, do not contribute centrosomes to zygotes, it is still unknown whether freeze-dried spermatozoa in other mammals are fertile. Rabbit sperm was selected as a model because of its similarity to human sperm (considering the centrosome inheritance pattern). Freeze- drying induces rabbit spermatozoa to undergo dramatic changes, such as immobilization, membrane breaking, and tail fragmentation. Even when considered to be "dead" in the conventional sense, rabbit spermatozoa freeze-dried and stored at ambient temperature for more than 2 yr still have capability comparable to that of fresh spermatozoa to support preimplantation development after injection into oocytes followed by activation. A rabbit kit derived from a freeze-dried spermatozoon was born after transferring 230 sperm-injected oocytes into eight recipients. The results suggest that freeze-drying could be applied to preserve the spermatozoa from most other species, including human. The present study also raises the question of whether rabbit sperm centrosomes survive freeze-drying or are not essential for embryonic development.