Guy Ringler - Academia.edu (original) (raw)

Papers by Guy Ringler

American journal of obstetrics and gynecology, 2005

To determine how the type of embryo fragmentation on day 3 affects progression of human embryos t... more To determine how the type of embryo fragmentation on day 3 affects progression of human embryos to blastocyst and pregnancy rates following embryo transfer. Retrospective analysis of all in vitro fertilization cycles in patients < or =40 years of age or younger from January 2002 through December 2003, during which time surplus day 3 embryos were transferred to blastocyst medium for extended culture. All embryos (4 cells or more) not suitable for transfer or freezing 72 hours following in vitro fertilization were placed into microdroplets (60 microL) of blastocyst medium and cultured for an additional 48 hours to assess blastocyst formation. Normal blastocyst development required blastulation, a visible inner-cell mass, trophectoderm cells covering 60% of the inner zona surface and thinning of the zona. The rate of blastocyst formation was then analyzed (chi 2 and analysis of variance) against the type of fragmentation 72 hours after insemination. Pregnancy outcomes were analyzed ...

Fertility and Sterility, 2014

To identify determinants of blastocyst yield, implantation rate, and pregnancy outcome. Retrospec... more To identify determinants of blastocyst yield, implantation rate, and pregnancy outcome. Retrospective analysis of outcomes of 1,653 cycles of IVF. Private infertility clinic. Couples presenting to an infertility clinic for IVF. None. Blastocyst yield, implantation rate, and pregnancy. Of a broad array of potential determinants, only the total numbers of oocytes retrieved and properties of day 3 embryos were consistently predictive of blastocyst formation. Relative to numbers of oocytes fertilized by intracytoplasmic sperm injection (ICSI), yields of quality blastocysts were highest in cycles in which &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 oocytes were retrieved. Blastocyst yield was closely linearly correlated with average numbers of blastomeres in embryos on day 3. As oocyte yields rose, average grades and the implantation potential of the blastocysts selected for transfer increased by approximately 0.015 and 0.15%, respectively, for each additional oocyte. Independently, the implantation potential of blastocysts decreased 1.1% for each advancing year in age of the oocyte provider, and, for autologous transfers, uterine receptivity declined an additional 0.6% per year. Higher yields of blastocysts from cycles with high oocyte numbers afforded better selection of blastocysts for transfer, supporting higher overall implantation and pregnancy rates. While the proportion of fertilized oocytes that progressed to quality blastocysts diminished as numbers of recovered oocytes rose, rates of implantation and pregnancy after transfer of the selected best blastocysts increased. The age of the oocyte provider and oocyte yields independently impacted blastocyst implantation potential and uterine receptivity after controlled ovarian hyperstimulation, ICSI, and blastocyst transfer.

Molecular and Cellular Endocrinology, 1989

There is little information on the molecular events underlying the effects of cAMP on human chori... more There is little information on the molecular events underlying the effects of cAMP on human chorionic gonadotropin (hCG) and particularly steroidal hormone production in normal trophoblasts. We examined the effects of 8-bromo-cAMP on mRNAs encoding two components of the cholesterol side-chain cleavage system, cytochrome P-450scc and adrenodoxin, and the alpha- and beta-subunits of hCG in cultured cytotrophoblasts. cAMP caused an increase in all of these mRNAs within 24 h, whereas actin mRNA declined. alpha-hCG mRNA increased first, followed by adrenodoxin, beta-hCG and cytochrome P-450scc mRNAs. The effects of 8-bromo-cAMP on alpha- and beta-hCG, adrenodoxin, and cytochrome P-450scc mRNAs, in cytotrophoblasts and JEG-3 choriocarcinoma cells, required the catalytic unit of protein kinases since H-7, a kinase inhibitor, blocked the increase in the mRNAs and prevented the stimulation of hCG and progesterone secretion. 8-Bromo-cAMP promoted a rapid increase in alpha-hCG mRNA in cytotrophoblasts in the presence of cycloheximide, an inhibitor of protein synthesis. In cytotrophoblasts, cycloheximide reduced basal and 8-bromo-cAMP-stimulated adrenodoxin mRNA abundance. In contrast, basal and cAMP-stimulated adrenodoxin mRNA was augmented by cycloheximide in JEG-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Fertility and Sterility, 2011

CASE REPORT: A 34 year old female gravida 2, para 1011, presented to our clinic with secondary am... more CASE REPORT: A 34 year old female gravida 2, para 1011, presented to our clinic with secondary amenorrhea and severe, progressive hirsutism. On clinical examination she was noted to have severe hirsutism and male-pattern scalp balding. Laboratory results showed severe hyperandrogenemia, with an elevated total testosterone (T) level of 140 ng/dL (reference value in our laboratory is 0-80 ng/dL) and androstenedione of 272 ng/dL (reference value of 30-250 ng/dL). CT of the abdomen and pelvis showed normal adrenal glands. Pelvic ultrasound and MRI of the pelvis demonstrated mildly prominent ovaries, containing numerous small follicles around the periphery. Catheterization and selective blood sampling from bilateral ovarian veins was performed. Results demonstrated excessive androgen production from the right ovary. The patient underwent an uncomplicated laparoscopic right salpingo-oophorectomy. Careful microscopic analysis of 2 mm slices of the ovary failed to demonstrate any tumor. Postoperatively the patient had mild subjective improvement in symptoms. However, her T levels did not appreciably decrease (postoperative T 136 ng/dL). CONCLUSION(S): This case demonstrates surprising preferential androgen secretion from one ovary in a hyperandrogenic disorder that involved both ovaries in excessive androgen production. The most likely diagnosis is hyperthecosis or so called ''HAIRAN''-syndrome. Though frustrating for both the patient and provider, this case serves as an excellent review of the differential diagnosis, analysis, and interpretation of androgens of ovarian and adrenal origin.

Fertility and Sterility, 2006

To determine whether elements of treatment associated with faster doubling times of total beta-hC... more To determine whether elements of treatment associated with faster doubling times of total beta-hCG in serum (beta-t2) in pregnant patients are also associated with a higher likelihood of pregnancy in all patients. Retrospective analysis of beta-t2 values, elements of ovarian stimulation (COH), and outcomes. Private assisted reproductive technology (ART) center. Initial analysis of data from 432 cycles in which conception occurred after COH and embryo transfer, followed by analysis of pregnancy outcomes after 1,287 cycles of COH/ embryo transfer. No interventions. The beta-t2 values initially computed from consecutive serum beta-hCG levels in ongoing pregnancies were correlated with multiple properties of the patients and their treatment cycles. The beta-t2 values during early pregnancy increased exponentially from about 1.6 days at 12 days to about 3.0 days at 24 days after embryo transfer. In those pregnancies which spontaneously aborted, early average beta-t2 values were higher than those for ongoing pregnancies; absolute beta-hCG levels did not differ. Positive correlations were established between beta-t2 values, the number of days of stimulation, and the number of ampules of drug administered per oocyte retrieved. The beta-t2 values were inversely related to average numbers of blastomeres in transferred embryos. Ongoing pregnancy rates (PR) were higher for cycles with lower gonadotropin dosages per oocyte retrieved, and when the average number of blastomeres in transferred embryos was higher. Steeper beta-hCG doubling times in early pregnancy were associated with lower gonadotropin dosages during ovarian stimulation and with higher numbers of blastomeres in transferred embryos. The latter variables were, in turn, associated with a higher likelihood of pregnancy after embryo transfer.

Endocrinology, 1989

Steroid hormones are thought to play a role in controlling placental endocrine function. Since ma... more Steroid hormones are thought to play a role in controlling placental endocrine function. Since maternal free cortisol levels increase during gestation, and glucocorticoid receptors have been identified in placental tissue, we examined the effects of glucocorticoids on the production of CG by cultured human cytotrophoblasts. Treatment of cytotrophoblasts with 1 microM dexamethasone increased CG secretion by 6- to 10-fold over a 72-h period, whereas progesterone (1 microM) had no effect. The stimulatory effects of dexamethasone were blocked by the glucocorticoid antagonist RU 486, indicating a requirement for the glucocorticoid receptor. Intracellular accumulation of the CG alpha-subunit in response to dexamethasone was demonstrated by immunocytochemistry, and Northern blot analyses revealed that dexamethasone treatment increases CG alpha- and beta-subunit mRNA levels. Dexamethasone also enhanced the stimulatory effects of 8-bromo-cAMP on CG secretion. We conclude that glucocorticoids as well as cAMP modulate human trophoblast endocrine functions.

American Journal of Obstetrics and Gynecology, 1993

ABSTRACT Objectives: We determined the effect of embryo transfer, zygote intrafallopian transfer,... more ABSTRACT Objectives: We determined the effect of embryo transfer, zygote intrafallopian transfer, and frozen embryo transfer on clinical outcomes after surrogate gestational transfers. Study Design: Prospective randomization was carried out. Results: Forty-five infertile couples were matched with a gestational surrogate carrier and underwent 81 cycles of embryo transfer with various assisted reproductive technologic procedures. Nineteen cycles produced a clinical pregnancy, with delivery in 15 of 81 cycles (18.5% live-birth rate). Fifteen of the 45 couples (33%) had a child from the surrogate gestational carrier program. Conclusion: No significant differences in clinical outcome were observed on the basis of the type of procedure performed or the age of the patient.

American Journal of Obstetrics and Gynecology, 1989

Colony-stimulating factor 1 is a hematopoietic growth factor that increases 1000-fold in the uter... more Colony-stimulating factor 1 is a hematopoietic growth factor that increases 1000-fold in the uteri of pregnant mice, and its receptor is abundantly expressed in the human placenta. The concentration of colony-stimulating factor 1 in amniotic fluid at 33 to 40 weeks (9.0 +/- 1.1 ng/ml) was twofold higher than that at 16 to 18 weeks gestation (4.1 +/- 0.5 ng/ml), whereas maternal serum colony-stimulating factor 1 levels did not rise significantly. Colony-stimulating factor 1 was detected in endometrial extracts from pregnant women and levels were higher than those in extracts from nonpregnant women.

American Journal of Obstetrics and Gynecology, 1999

Our aim was to determine which factors influence the effectiveness of intrauterine insemination. ... more Our aim was to determine which factors influence the effectiveness of intrauterine insemination. This article is a retrospective statistical analysis of outcomes of 9963 consecutive intrauterine insemination cycles. Patient age was the main determinant of pregnancy outcome (analysis of variance F ratio = 29, P <.0001), followed by the number of follicles at the time of intrauterine insemination (analysis of variance F ratio = 9, P <.0001) and sperm motility in the inseminate (analysis of variance F ratio = 4, P =.002). A total of 18.9% of all patients <26 years old conceived, compared with 13.9% of those 26-30 years old, 12.4% of those 31-35 years old, 11.1% of those 36-40 years old, 4.7% of those 41-45 years old, and 0.5% of patients >45 years old (P <.001). When analyzed by single years, ongoing pregnancy rates after intrauterine insemination remained high through age 32 years. Across all ages and causes of infertility, 7.6% of patients with 1 follicle at the time of intrauterine insemination conceived, compared with 10. 1% with 2, 14.0% with 4, and 16.9% with 6 follicles (P <.01). When ovulation occurred before intrauterine insemination (ie, no visible follicular structures), 4.6% of patients conceived. The likelihood of pregnancy was maximized when motile sperm numbers were >/=4 million and sperm motility was >/=60%. Differences in pregnancy outcomes between sperm processing options were related to differences in sperm motility after processing; use of methods incorporating motility enhancement with pentoxifylline and motile sperm concentration through silica gradients yielded the highest overall pregnancy rates. When the results of ongoing retrospective analysis of intrauterine insemination outcomes are applied, overall intrauterine insemination pregnancy rates have increased from 5.8% per cycle in 1991 to 13.4% per cycle in 1996, during which time the average age of patients undergoing intrauterine insemination has increased from 36.1 (+/-0.2) to 39.2 (+/-0.1) years.

American Journal of Obstetrics and Gynecology, 2005

Objective(s): To determine how the type of embryo fragmentation on day 3 affects progression of h... more Objective(s): To determine how the type of embryo fragmentation on day 3 affects progression of human embryos to blastocyst and pregnancy rates following embryo transfer. Study design: Retrospective analysis of all in vitro fertilization cycles in patients %40 years of age or younger from January 2002 through December 2003, during which time surplus day 3 embryos were transferred to blastocyst medium for extended culture. All embryos (4 cells or more) not suitable for transfer or freezing 72 hours following in vitro fertilization were placed into microdroplets (60 mL) of blastocyst medium and cultured for an additional 48 hours to assess blastocyst formation. Normal blastocyst development required blastulation, a visible inner-cell mass, trophectoderm cells covering 60% of the inner zona surface and thinning of the zona. The rate of blastocyst formation was then analyzed (c 2 and analysis of variance) against the type of fragmentation 72 hours after insemination. Pregnancy outcomes were analyzed with respect to the pattern of fragmentation in cleaving embryos transferred after 3 days of culture. Results: A total of 1566 embryos were cultured beyond day 3 of development of which 229 (14.6%) reached the blastocyst stage and were frozen. Embryos exhibiting no fragmentation or type I fragmentation had significantly higher blastocyst development rates (27.9% and 19.9%) than embryos with type 2 or 3 fragmentation (13.9 and 8.8, respectively; P ! .001). No embryos with type 4 or 5 fragmentation progressed to blastocyst. The average type of fragmentation in transferred embryos correlated with pregnancy outcome and embryo age. Conclusion(s): More pervasive embryo fragmentation was associated with a decreasing rate of blastocyst development with day 3 embryos. To the extent that blastocyst development rates of day 3 embryos is an index of embryo viability, our findings establish that careful classification of the type of embryo fragmentation is important in selection of day 3 embryos for transfer. Recent reports of associations among embryo fragmentation, aneuploidy, apoptosis, and patient age support these conclusions.