The effectiveness of flow cytometric sorting of human sperm (MicroSort®) for influencing a child's sex.

BACKGROUND: Flow cytometric sorting can be used to separate sperm based on sex chromosome content. Differential fluorescence emitted by stained X- vs. Y-chromosome-bearing sperm enables sorting and collection of samples enriched in either X- or Y-bearing sperm for use to influence the likelihood that the offspring will be a particular sex. Herein we report the effectiveness of flow cytometric sorting of human sperm and its use in human ART procedures. METHODS: This prospective, observational cohort study of the series of subjects treated with flow cytometrically sorted human sperm was conducted at investigational sites at two private reproductive centers. After meeting inclusion criteria, married couples (n = 4993) enrolled to reduce the likelihood of sex-linked or sex-limited disease in future children (n = 383) or to balance the sex ratio of their children (n = 4610). Fresh or frozen-thawed semen was processed and recovered sperm were stained with Hoechst 33342 and sorted by flow cytometry (n = 7718) to increase the percentage of X-bearing sperm (n = 5635) or Y-bearing sperm (n = 2083) in the sorted specimen. Sorted sperm were used for IUI (n = 4448) and IVF/ICSI (n = 2957). Measures of effectiveness were the percentage of X- and Y-bearing sperm in sorted samples, determined by fluorescence in situ hybridization, sex of babies born, IVF/ICSI fertilization- and cleavage rates, and IUI, IVF/ICSI, FET pregnancy rates and miscarriage rates. RESULTS: Sorted specimens averaged 87.7 ± 5.0% X-bearing sperm after sorting for X and 74.3 ± 7.0% Y-bearing sperm after sorting for Y. Seventy-three percent of sorts were for girls. For babies born, 93.5% were females and 85.3% were males after sorting for X- and Y-bearing sperm, respectively. IUI, IVF/ICSI, and FET clinical pregnancy rates were 14.7%, 30.8%, and 32.1%, respectively; clinical miscarriage rates were 15.5%, 10.2%, and 12.7%. CONCLUSIONS: Flow cytometric sorting of human sperm shifted the X:Y sperm ratio. IUI, IVF/ICSI and FET outcomes were consistent with unimpaired sperm function. Results provide evidence supporting the effectiveness of flow cytometric sorting of human sperm for use as a preconception method of influencing a baby's sex. TRIAL REGISTRATION: NCT00865735 (ClinicalTrials.gov).

Further comment on the House of Commons' report Human Reproductive Technologies and the Law.

The Fifth Report by the Science and Technology Committee of the House of Commons advances majority positions which often are highly supportive of reproductive liberty. This was, however, achieved with considerable difficulty and involved numerous compromises with a minority favouring intrusion by the state into reproductive matters. The report identifies examples of regulatory overreach in such areas as gender selection and gamete donation. The report is available on the internet and deserves to be widely read both at home and abroad. It merits being honoured not only for the nobility of some of its expressions, but more significantly to the extent that it proves effective in enhancing the protection of reproductive freedom from creeping statism and arbitrary regulation.

Scientific aspects of preconception gender selection.

Although numerous methods have been promoted as having an influence on the gender of offspring, most lack credible scientific evidence of effectiveness. Preconception gender selection has an important application in reducing the risk of having children with X-linked disease. A preconception, flow cytometric sperm sorting method of gender selection (MicroSort) is based upon the detection of differential fluorescence emitted by fluorescently stained X and Y chromosome-bearing spermatozoa. Ongoing clinical trial results illustrate the safety and efficacy of the method. Fluorescence in-situ hybridization (FISH) analysis of specimens pre- and post-sort show the 50:50 X:Y ratio in unsorted spermatozoa can be shifted to 90% X or 75% Y after sorting. Embryo gender and fetal/baby gender are consistent with post-sort FISH results. Intrauterine insemination (IUI) and IVF/ICSI (intracytoplasmic sperm injection) pregnancy rates are consistent with those reported in the assisted reproduction literature. Clinical loss rates are similar to those in the general population. The observed major congenital abnormality rate of 2.05% for babies born after using this sperm sorting method coincides with that occurring spontaneously. Current results indicate that the method is a safe and effective process and is a valuable tool for families wishing to balance the gender distribution of their children or to reduce the likelihood of having children with X-linked disease.

An attempted suppression of liberty.

The Human Fertilisation and Embryology Authority (HFEA) report on gender selection is a presumptuous, biased, and misguided attempt to provide a basis on which to deny the freedom to make their own reproductive choices to citizens of Great Britain. The report should be soundly rejected.

Non-disclosing preimplantation genetic diagnosis for Huntington disease.

OBJECTIVES: Individuals at risk for Huntington disease face difficult decisions regarding their reproductive options. Most do not wish to pass on the gene for Huntington disease to their children, but may not be prepared themselves to undergo presymptomatic testing and learn their genetic status. For these reasons, many at-risk individuals with a family history of HD would choose a method of genetic diagnosis that would assure them that they can have children unaffected with HD without revealing their own genetic status (non-disclosing). We have shown that, with a carefully designed and executed programme of non-disclosing preimplantation genetic testing, one can successfully assist at-risk couples to have their own biological children who are free from Huntington disease, without forcing parents to confront knowledge of their own genetic status. METHODS: Couples where one partner was at 50% risk for Huntington disease underwent in vitro fertilization with preimplantation embryo biopsy and molecular analysis for Huntington disease where appropriate. RESULTS: After extensive counselling and informed consent, 10 couples underwent 13 in vitro fertilization and two frozen embryo transfer cycles in a programme for non-disclosing preimplantation genetic diagnosis for Huntington disease. In 11 cycles, embryos determined to be free of Huntington disease were transferred, resulting in five clinical pregnancies. One set of twins and three singleton pregnancies have delivered. One pregnancy resulted in a first-trimester loss. CONCLUSIONS: The option of non-disclosing preimplantation genetic diagnosis should be reviewed, along with other relevant medical options, when counselling at-risk Huntington disease families.

Aggressive outpatient treatment of ovarian hyperstimulation syndrome with ascites using transvaginal culdocentesis and intravenous albumin minimizes hospitalization.

PURPOSE: To assess the effectiveness of outpatient treatment of Ovarian Hyperstimulation Syndrome associated with ascites. METHODS: Forty-eight patients diagnosed with ovarian hyperstimulation and ascites from 2,246 consecutive in vitro fertilization cycles were retrospectively studied. Patients were treated with outpatient transvaginal culdocentesis and rehydration with intravenous crystalloids and albumin every 1-3 days until resolution of symptoms or hospitalization was required. Outcomes measured included incidences of hospitalization, pregnancy outcomes, cycle characteristics, and oocyte donors versus nondonors comparisons. RESULTS: No complications occurred from outpatient treatments, and 91.6% of patients avoided hospitalization. The pregnancy rate in patients undergoing transfer was 84.7%, and the spontaneous loss rate was 16%. Overall, the estradiol on day of hCG was 4331 pg/mL (range 2,211-8,167), ascites removed was 1910 cm3 (122-4,000), and number of outpatient treatments was 3.4 (1-14). Nondonors averaged more outpatient treatments than donors (3.97 vs. 1.85), but similar rates of hospitalization (3/35 vs. 1/13). CONCLUSIONS: Outpatient treatment consisting of culdocentesis, intravenous rehydration, and albumin minimized the need for hospitalization in hyperstimulated patients.