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Biomedical subjects

Norbert Gleicher

Publications and source records attributed to Norbert Gleicher.

At least 19 recordsLinked to original sources

"Ovarian age-based" stimulation of young women with diminished ovarian reserve results in excellent pregnancy rates with in vitro fertilization.

OBJECTIVE: To determine whether pregnancy outcome can be positively affected if the ovarian stimulation in women with diminished ovarian reserve (DOR) is changed. DESIGN: Case control study. SETTING: Medical school-affiliated private infertility center. PATIENT(S): Sixty-two women, aged 26-35 years, with the diagnosis of DOR (study group) and 62 age-matched controls with apparently normal ovarian function (control group). INTERVENTION(S): Study group patients received a modified (ovarian age-based) stimulation with microdose GnRH agonist (GnRH-a) and 450-600 IU of gonadotropin daily. Women in the control group received a standard "chronological age-based" stimulation with long luteal phase GnRH-a and up to 300 IU of gonadotropins (two patients in this group received an antagonist in place of an agonist). MAIN OUTCOME MEASURE(S): The IVF cycle outcome parameters, including pregnancy rates (PR). RESULT(S): Women with DOR and controls did not differ significantly in patient profiles or underlying infertility conditions and received identical embryo numbers at transfer. The DOR patients demonstrated a strong trend toward lower gravidity. Peak E(2) levels were similar between groups but controls produced significantly more oocytes, a strong trend toward more embryos and significantly more cycles of cryopreservation. Both groups achieved a 47% rate of first positive pregnancy test (hCG), with controls demonstrating a 39% and DOR patients a 32% ongoing PR. CONCLUSION(S): Women with DOR, if treated with an ovarian age-based rather than chronological age-based ovarian stimulation protocols, will demonstrate surprisingly good PR with IVF in comparison to women with normal ovarian function.

Adult↗

The impact of abnormal autoimmune function on reproduction: maternal and fetal consequences.

The impact of abnormal autoimmune function on reproductive success has remained a highly controversial issue. This is, at least partially, due to the relative lack of demographic data from women with established autoimmune diseases. We, therefore, investigated 163 women with proven autoimmune diseases and 73 controls in a demographic study of reproductive success and impact of abnormal autoimmunity on pregnancy and offspring. Women with autoimmune diseases experienced fewer pregnancies overall (p=0.04) and fewer pregnancy losses (p=0.05). Offspring from women with autoimmune diseases demonstrated a significantly increased prevalence of confirmed autoimmune diseases (p=0.04; OR 3.759; 95%CL 1.04-1.27), which increased further if suspected, but not yet confirmed, cases were added (p=0.001; OR 8.592; 95%CL 1.05-55.0). Women with autoimmune diseases exhibited a trend towards lower cesarean section delivery during their own birth and a significantly increased prevalence of disease in vaginally delivered offspring (p=0.014; OR 6.041; 95%CL 1.32-38.22). Autoimmune diseases impair female fecundity even before the diseases become clinically overt. Offspring are at increased risk to develop autoimmune diseases, though they may differ from those of their mothers. This risk appears to correlate with mode of delivery and may be the consequence of varying cell traffic dynamics with vaginal and cesarean section deliveries.

Adult↗

Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF.

BACKGROUND: The aim of this study was to investigate the effect of treatment with dehydroepiandrosterone (DHEA) on fertility outcomes among women with diminished ovarian reserve. MATERIALS AND METHODS: This is a case-control study in an academically affiliated private infertility centre. Twenty-five women with significantly diminished ovarian reserve had one IVF cycle before and after DHEA treatment, with otherwise identical hormonal stimulation. Women received 75 mg of DHEA daily (25 mg three times daily) for an average of 17.6 +/- 2.13 weeks. We performed a comparison of IVF outcome parameters, before and after DHEA treatment, including peak estradiol (E(2)) levels, oocyte and embryo numbers, oocyte and embryo quality and embryo transfer statistics. RESULTS: Paired analysis of IVF cycle outcomes in 25 patients, who underwent cycles both before and after DHEA supplementation, demonstrated significant increases in fertilized oocytes (P < 0.001), normal day 3 embryos (P = 0.001), embryos transferred (P = 0.005) and average embryo scores per oocyte (P < 0.001) after DHEA treatment. CONCLUSION: This study confirms the previously reported beneficial effects of DHEA supplementation on ovarian function in women with diminished ovarian reserve.

Dehydroepiandrosterone↗

A formal comparison of the practice of assisted reproductive technologies between Europe and the USA.

In this study, we compared pregnancy and delivery outcomes after the utilization of assisted reproductive technologies (ART) in Europe and the United States (US). ART outcomes were compared between Europe and the US for the year 2001, based on formal reports published by the European Society for Human Reproduction and Embryology (ESHRE) and the Center for Disease Control and Prevention (CDC) in collaboration with the American Society for Reproductive Medicine (ASRM) and Society for ART (SART). Europe utilizes ART at approximately twice the rate of the US (P < 0.001). United States patients showed a significantly decreased likelihood of reaching oocyte retrieval (P < 0.001) and embryo transfer (P < 0.001). Despite this lower chance of reaching oocyte retrievals and embryo transfers, US patients experienced significantly higher clinical pregnancy rates (P < 0.001) and delivery rates per started cycle (P < 0.001) than European patients. Amongst patients reaching oocyte retrieval, the difference in clinical pregnancy rates and live birth rates was even more pronounced in favour of the US. However, US patients received significantly more embryos per embryo transfer (P < 0.001) and experienced a significantly higher multiple pregnancy rate (P < 0.001). Significant differences in favour of US patients in pregnancy rates and live birth rates were also observed for frozen embryo cycles and oocyte donation cycles, where the difference was most pronounced. The better pregnancy and live birth outcomes in the US are not explainable by the transfer of larger embryo numbers alone.

Adult↗

The relative myth of elective single embryo transfer.

The option of single embryo transfer (SET) has recently dominated the pages of this and other medical journals. Opinions, in regards to the utility of such an approach, appear to differ between Europe and the US. While US guidelines promote a more individualized approach, European opinions, at times, even advocate mandated practice patterns. The European approach, however, fails to recognize the rather significant differences in supportive arguments between the historical switch from multiple embryo transfers to 2-embryo transfers and the current discussion, favouring a switch from 2-embryo transfer to elective (e)-SET. In the former, a significant risk of (at times, high-order) multiple pregnancies was reduced without loss of pregnancy potential. In the latter, a comparably relatively low twinning risk is reduced at the expense of declining pregnancy rates, a need for more treatment cycles, a potential delay in treatment success and, potentially, higher treatment costs. These consequences of e-SET, together with the preference of some infertility patients to actually conceive twins, raise serious questions about the wide utilization of e-SET, as has been propagated by many authorities. According to US guidelines, e-SET, therefore, appears to represent an appropriate transfer option for only a small minority of IVF patients. Argument in favour of indiscriminate SET appears unrealistic and should be reconsidered.

Cost-Benefit Analysis↗

An evolutionary concept of polycystic ovarian disease: does evolution favour reproductive success over survival?

Polycystic ovarian disease (PCOD) is currently considered as possibly the most frequent cause of female infertility. It is also closely associated with syndrome XX, which, in turn, is closely linked with premature and excessive mortality. Considering these adverse effects on reproductive success and human survival, the evolutionary survival of PCOD, itself considered by many to be a genetically transmitted condition, would, on first glance, appear surprising, since evolution usually discriminates against both of these traits. However, an analysis of some recently reported characteristics of the condition calls for the reconsideration of PCOD as a condition which, from an evolutionary viewpoint, favours decreased reproductive success. Indeed, the reported observations that patients with PCOD will resume spontaneous ovulation with even relatively minor weight loss, and experience later menopause than controls, suggests exactly the opposite. Under an evolutionary concept, PCOD can thus be seen as a 'fertility storage condition' which in fact favours human reproductive success and allows the human species to maintain fertility even during adverse environmental circumstances, such as famines.

Anovulation↗

Increased oocyte production after treatment with dehydroepiandrosterone.

OBJECTIVE: To describe a case of dramatically improved ovarian reserve in a 42.7-year-old woman who was using the dietary supplement dehydroepiandrosterone (DHEA) as well as acupuncture. DESIGN: Case report. SETTING: Private IVF center. PATIENT(S): A 42.7-year-old patient with initial severely decreased ovarian reserve. INTERVENTION(S): Serial ovulation induction with concomitant use of DHEA dietary supplementation as well as acupuncture. MAIN OUTCOME MEASURE(S): Peak E2 concentration, oocytes retrieved, and cyropreservable embryos. RESULT(S): In her first treatment cycle peak E2 was 1,211 pmol/mL. After seven months of DHEA supplementation her peak E2 in cycle 8 was > 18,000 pmol/mL. Because of fear of hyperstimulation we reduced her gonadotropin stimulation by 25%. In the ninth cycle peak E2 was 9,178 pmol/mL, resulting in retrieval of 17 oocytes (16 embryos). In the last 11 months the patient has undergone nine treatment cycles while continuously and dramatically improving her ovarian response and banking of 66 embryos overall. CONCLUSION(S): This case illustrates the possibility that ovarian function may be salvaged, even in women of advanced reproductive age.

Adult↗

Blastomere transplantation in human embryos may be a treatment for single gene diseases.

OBJECTIVE: To determine whether human embryos accept blastomere transplants and integrate them normally into the architecture of the developing embryo. DESIGN: A human blastomere transplantation model, involving 44 cryopreserved embryos that were specifically donated to research. SETTING: Academically affiliated private infertility center. PATIENT(S): Forty-four human embryos. INTERVENTION(S): In 21 experiments, one, two, or three blastomeres were transplanted, using standard microsurgical techniques that are widely used in preimplantation genetic diagnosis (PGD). Embryos were thawed and gender was determined, using established PGD techniques. Male (xy) blastomeres were then transplanted into female (xx) day 3 embryos, and the xy cells were tracked through blastocyst stage (days 5-6) and into the hatching period (day 6), using fluorescent in situ hybridization (FISH). MAIN OUTCOME MEASURE(S): Degree and location of xy cell integration into xx embryos. RESULT(S): High-quality recipient embryos (with 4 to 10 cells) developed uniformly into normal blastocyst stage embryos in 12 of 12 experiments (100%) and integrated donor blastomeres into their architecture, with apparently even distribution of daughter cells; this integration was documented in inner cell mass as well as in trophoectoderm. The intensity of this distribution appeared to correlate with the number of blastomeres transferred. Among nine abnormally developing embryos, only three (33%) demonstrated a normal distribution of offspring donor cells. CONCLUSION(S): High-quality embryos appear to have the ability to integrate donor blastomeres. Because the treatment of single gene diseases does not require successful treatment of all cells, blastomere transplantation could be explored as a treatment option, which also would greatly enhance efficiency and utilization of preimplantation genetic diagnosis.

Blastocyst↗