Basil Ho Yuen

A comparison of sperm aneuploidy rates between infertile men with normal and abnormal karyotypes

BACKGROUND Abnormal semen parameters in chromosomally normal men are an indicator of an increased risk of sperm aneuploidy. Male carriers of chromosomal rearrangements may also display an increase in sperm aneuploidy for chromosomes not involved in the rearrangement, known as an interchromosomal effect (ICE), and this may be related to the impaired semen parameters of these men. METHODS Aneuploidy was examined in ejaculate sperm from 27 men: 8 carriers of chromosomal rearrangements with severe oligoasthenoteratozoospermia (OAT) or severe teratozoospermia; 10 chromosomally normal men with similarly abnormal semen parameters; and 9 proven fertile men with normal semen parameters. Fluorescence in situ hybridization was used to examine aneuploidy for chromosomes 13, 18, 21, X and Y. RESULTS We observed evidence of an ICE in three of the eight carriers of chromosomal rearrangements. However, men who were chromosomally normal but had severe OAT more frequently displayed increased disomy rates. Although autosomal disomy rates were only modestly increased in some of these men, increased XY disomy ranged from slight to extreme (up to a 100-fold increase). CONCLUSIONS Despite their similar semen parameters, infertile men with normal karyotypes displayed more frequent increases in sperm aneuploidy, particularly involving the sex chromosomes, than infertile men who were carriers of chromosomal rearrangements. The difference in the magnitude and type of sperm aneuploidy between the two infertile groups is likely related to the different causes of infertility.

The outcome of in vitro fertilization and embryo transfer in women with polycystic ovary syndrome failing to conceive after ovulation induction with exogenous gonadotropins

OBJECTIVE To assess the outcome of in vitro fertilization and embryo transfer (IVF-ET) in women with refractory polycystic ovarian syndrome (PCOS). DESIGN Retrospective case series with an age-matched control group. SETTING Ovulation induction and IVF programs in a tertiary referral center. PATIENTS AND INTERVENTIONS Nine patients with PCOS who failed standard ovulation induction treatment (clomiphene citrate plus greater than or equal to 6 ovulatory human menopausal gonadotropin [hMG] cycles) underwent 19 cycles of IVF-ET. Forty age-matched tubal factor patients who completed 40 cycles of IVF-ET served as a control group. OUTCOME MEASURES Demographic features and IVF-ET cycle characteristics were compared using Students t-test and Fishers exact test. RESULTS Cycles of IVF-ET in patients with PCOS were associated with higher estradiol levels (5,222 versus 4,009 pmol/L), lower hMG requirements (15.8 versus 19.6 vials), greater numbers of oocytes (7.6 versus 5.6), and lower fertilization rates (56% versus 75%) compared with tubal factor cycles (P less than 0.05). However, the number of embryos transferred (3.9 versus 4.0) and the clinical pregnancy rate per embryo transfer (24% versus 25%) did not differ significantly between the two groups. CONCLUSION These results suggest that conception failure after six or more ovulatory hMG cycles in patients with PCOS does not adversely affect subsequent IVF performance.

Plasma prolactin, human chorionic gonadotropin, estradiol, testosterone, and progesterone in the ovarian hyperstimulation syndrome☆

Plasma prolactin, estradiol, progesterone, and testosterone, but not HCG-beta levels, were higher in a patient who developed the ovarian hyperstimulation syndrome while undergoing ovulation induction with human gonadotropins than in two other women who also became pregnant after similar treatment without complications. These results suggest that hyperprolactinema, in association with elevated ovarian steroid levels, may be factors in the pathogenesis of this disorder.

Relationship of oral contraceptives and the intrauterine contraceptive devices to the regression of concentrations of the beta subunit of human chorionic gonadotropin and invasive complications after molar pregnancy

One hundred ninety-four patients with pathologically confirmed molar pregnancy and intact uteri were studied prospectively. Group A included 177 patients in whom the beta subunit of human chorionic gonadotropin (hCG-beta) declined to normal (less than 5 mlU/ml) without chemotherapy, whereas group B included 17 patients with invasive complications in the postmolar phase which necessitated the use of chemotherapy. Only women with intact uteri were included in the study. In group A, there were no significant differences in the human chorionic gonadotropin (hCG) positive interval between women who used intrauterine contraceptive devices, barrier and other methods, and those who used oral contraceptives. Differences in the proportions of women in groups A and B who used the oral contraceptives and intrauterine contraceptive devices were not observed. However, the mean dosage of estrogen and the proportion of women who ingested more than 50 micrograms of estrogen were higher in group B. These data suggest that (1) the oral contraceptives with less than 50 micrograms of estrogen and the intrauterine contraceptive devices do not prolong the hCG-beta positive interval nor increase the risk of invasive complications in the postmolar phase which requires the use of chemotherapy; and (2) the dose of estrogen (in formulations that contain more than 50 micrograms) rather than the oral contraceptives per se may influence the risk of these postmolar complications.

Relationship of gonadotropin-releasing hormone, danazol, and prostaglandin blockade to ovarian enlargement and ascites formation of the ovarian hyperstimulation syndrome in the rabbit

The effects of pharmacologic doses of gonadotropin-releasing hormone, danazol, and indomethacin on the clinical and endocrinologic features of the ovarian hyperstimulation syndrome were studied in the rabbit. The ovarian hyperstimulation syndrome was induced with Pergonal (75 IU of follicle-stimulating hormone and 75 IU of luteinizing hormone) and a follicle-stimulating hormone-dominant gonadotropin preparation (85 IU of follicle-stimulating hormone and 53 IU of luteinizing hormone). None of the three agents tested were effective in suppressing the ovarian enlargement and ascites formation in these animals. Ascites developed despite quite significant variations in plasma and intraovarian sex steroid hormone and intraovarian prostaglandin F levels induced by danazol and indomethacin. Ascites develops in hyperstimulated women in association with both follicular and luteal hyperstimulation. In contrast, the ascites response in the hyperstimulated rabbit develops in the presence of follicular hyperstimulation alone without a significant degree of luteal hyperstimulation.

Clinical, endocrinologic, and intraovarian prostaglandin F responses to H-1 receptor blockade in the ovarian hyperstimulation syndrome: studies in the rabbit model.

The effects of chlorpheniramine maleate, an H-1 receptor blocker, on clinical and endocrinologic features and intraovarian prostaglandin F (PGF) content were assessed in the rabbit model of the ovarian hyperstimulation syndrome. H-1 receptor blockade prevented ascites, attenuated ovarian enlargement (2.68 +/- 0.37 gm versus 4.15 +/- 0.056 gm; p less than 0.05), and augmented intraovarian PGF content (8.4 +/- 0.84 versus 3.95 +/- 1.12 pg/mg protein; p less than 0.05). Steroidogenesis was unaffected. In the control group, in which weights remained stable, animals with minimal ascites (scores less than or equal to 2; n = 4) were compared to other control animals with a greater accumulation of fluid (scores greater than or equal to 3; n = 4). The former also exhibited lower ovarian weights (2.94 +/- 0.41 versus 5.35 +/- 0.59 gm; p less than 0.05) and higher PGF ovarian content (6.05 +/- 1.56 versus 1.8 +/- 0.75 pg/mg of protein; p less than 0.05). This triad of minimal ascites, lower ovarian weights, and elevated intraovarian PGF seen both in treated animals and in inherently more resistant control animals did not appear to depend on changes in body weight. The conclusion reached was that H-1 receptor blockade prevented ascites, reduced ovarian enlargement, and augmented PGF content but did not affect steroidogenesis. This protective effect of chlorpheniramine may be mediated at least in part by prostaglandins.

Molar pregnancy in British Columbia: estimated incidence and postevacuation regression patterns of the beta subunit of human chorionic gonadotropin.

A total of 171 cases of molar pregnancy were followed by serial radioimmunoassay of the beta subunit of human chorionic gonadotropin (hCG-beta) over a 4-year period. The incidence over the study interval was 1:1,202 pregnancies in the province. In 120 women with intact uteri and measurable plasma levels of hCG-beta at the initiation of follow-up, the hormone remained detectable for up to 219 days (between 31 and 32 weeks) following evacuation, with 50% of patients remaining positive at 63 days (between 8 and 9 weeks). In five women undergoing hysterectomy, the hormone remained detectable for up to 112 days (between 15 and 16 weeks) postoperatively. In 92% of the cases, hCG-beta regressed to negative without chemotherapy. The prolonged presence of hCG in plasma after evacuation of the mole, regardless of the presence or absence of the uterus, points to persistence of molar tissue and its gradual rejection from uterine and extrauterine sites as a common phenomenon in the natural history of the uncomplicated postmolar course of this disease.

The ascites in the ovarian hyperstimulation syndrome does not originate from the ovary

OBJECTIVE To evaluate the direct ovarian contribution to ascites formation in the ovarian hyperstimulation syndrome (OHSS) in a rabbit model. DESIGN Prospective experimental study. SETTING Research center of a university teaching hospital. PARTICIPANTS New Zealand White rabbits. INTERVENTIONS Both ovaries of the rabbits in the experimental group were enclosed within a pouch developed from the surrounding peritoneum and mesosalpinx by microsurgery. Animals in the control group did not undergo any surgical intervention. Ovarian hyperstimulation was induced by alternate day equine chorionic gonadotropin and intermittent human chorionic gonadotropin (hCG). MAIN OUTCOME MEASURES Degree of ascites formation and the morphological and endocrinologic signs of ovarian hyperstimulation. RESULTS The serial plasma estradiol and progesterone levels, ovarian weights, and ascites response were not statistically different between the two groups. CONCLUSIONS Isolation of both ovaries from the peritoneal cavity does not prevent ascites formation in the OHSS. Increased transudation across extraovarian serosal surfaces contributes to ascites formation in OHSS.

Cytogenetic investigation of fetuses and infants conceived through intracytoplasmic sperm injection.

OBJECTIVE To determine the incidence of aneuploidy among fetuses and infants conceived through intracytoplasmic sperm injection (ICSI) in our clinic using umbilical cord blood samples. DESIGN Follow-up study of the cytogenetic outcome of ICSI pregnancies. SETTING University-based IVF clinic. PATIENT(S) Forty-six couples who underwent ICSI and conceived. INTERVENTION(S) Umbilical cord blood was taken after delivery of the infant for analysis. Samples of chorionic villi and chorion were taken for studies on the spontaneous abortuses. Amniocentesis was performed for couples that chose prenatal diagnosis. MAIN OUTCOME MEASURE(S) The cytogenetic chromosomal status of the pregnancy outcome. RESULT(S) Fifty pregnancies and 55 live births were recorded, with nine spontaneous abortions. Of 43 separate umbilical cord blood samples analyzed, 1 abnormality (2%) was found, 45, XX,+21. Nine births went through prenatal diagnosis alone, with four accepting both forms of analysis-no abnormalities were found. Origin of abnormality was established in two spontaneous abortion cases (45, XO and 45, XY,-21), and the maternal chromosome was lost in both cases. CONCLUSION(S) Using umbilical cord blood obtained after birth, we obtained karyotype results from 78% of the ICSI population in our clinic. Combined with results from five additional cases that underwent prenatal diagnosis but not umbilical cord blood sampling, a chromosomal result was obtained in 87% of our ICSI population. The use of umbilical cord blood for cytogenetic analysis substantially improves the ability to determine rates of chromosomal abnormalities in newborns produced via ICSI clinics.

Chromosome investigation in in vitro fertilization failure

PurposeA chromosomal complement of 227 human oocytes was studied to provide information on the frequency and type of chromosomal abnormalities in oocytes failing in vitro fertilization.ResultsNormal haploid chromosome complement was found in 54.6%; chromosomal abnormalities consisting of diploid sets were identified in 16.7% and aneuploidy was observed in 26%. Premature condensation of sperm chromosomes of the G1-phase was observed in 22.9% oocytes. Male infertility was correlated with an increase in the rate of aneuploidy when compared with tubal infertility. The rate of chromosome abnormalities for the oocytes recovered from women who had no fertilized oocytes was significantly higher compared to those with at least one oocyte fertilized.ConclusionA high frequency of chromosome abnormalities in unfertilized oocytes suggests that natural selection against chromosome abnormalities may occur even prior to fertilization.