Cecilia L. Schmidt

Transfer of cryopreserved-thawed embryos: the natural cycle versus controlled preparation of the endometrium with gonadotropin-releasing hormone agonist and exogenous estradiol and progesterone (GEEP)

Modeled on our successful experience with oocyte donation, we present a novel, viable approach to cryopreserved-thawed embryo transfers (ETs) in women with recalcitrant ovarian dysfunction: gonadotropin-releasing hormone agonist and exogenous estradiol and progesterone (GEEP). After attainment of ovarian suppression, seven such women received physiological steroidal replacement regimens with cryopreserved-thawed ETs prospectively synchronized with the 4th day of progesterone administration and two conceived. These GEEP cycles and cryopreserved-thawed ETs were prospectively compared with cryopreserved-thawed ETs performed on the 4th day of exposure to progesterone in 20 spontaneous cycles and in 5 oocyte donation-steroidal replacement cycles. Pregnancies occurred after three cryopreserved-thawed ETs in each of these groups. We conclude that GEEP constitutes a successful preparation for cryopreserved-thawed ETs, at the least, in women with ovulatory dysfunction.

GONADOTROPIN-RELEASING HORMONE AGONIST IMPROVES THE EFFICIENCY OF CONTROLLED OVARIAN HYPERSTIMULATION/INTRAUTERINE INSEMINATION

OBJECTIVEnLeuprolide acetate (LA) has improved the efficiency of human menopausal gonadotropins (hMG) in in vitro fertilization cycles. We hypothesized that the combination of LA/hMG/intrauterine insemination (IUI) would be more efficacious than hMG/IUI cycles.nnnDESIGNnDuring an 18-month period, all patients completing either a hMG/IUI cycle (group I) or a LA/hMG/IUI cycle (group II) had the characteristics and outcomes of their stimulation cycles assessed. The groups were not prospectively randomized.nnnSETTINGnReferral center at a tertiary care hospital.nnnPATIENTSnOne hundred twenty three patients in group I completed 219 cycles, and 64 patients in group II completed 102 cycles. Twenty-eight of the patients who failed to conceive with hMG/IUI were advanced to group II.nnnMAIN OUTCOME MEASURESnPregnancy/IUI is compared between the two groups.nnnRESULTSnGroup II demonstrated significantly greater clinical pregnancy/IUI than group I (26.5% and 16.0%, respectively, P less than 0.05), as well as a higher live birth/IUI (21.6% and 12.8%, respectively, P less than 0.05). No difference was present in the rate of fetal wastage or multiple births.nnnCONCLUSIONSnIn our patients with recalcitrant infertility, the addition of a gonadotropin-releasing hormone agonist to hMG/IUI improved the pregnancy rate, without increasing the rate of multiple births or fetal wastage.

Human chorionic gonadotropin stimulation of relaxin secretion by luteinized human granulosa cells

OBJECTIVEnTo determine the effect of human chorionic gonadotropin (hCG) on relaxin secretion by long-term cultures of luteinized human granulosa cells (GC).nnnDESIGNnLuteinized human GC were collected from 10 women undergoing in vitro fertilization (IVF) cycles. Luteinized human GC from each woman were plated in replicate wells at 1 x 10(5) cells/well and exposed to medium 199 (GIBCO, Grand Island, NY), medium 199 with 1 IU/mL hCG, and/or medium 199 with 100 IU hCG/mL. Luteinized human GC were maintained for up to 40 days in culture. Spent media were changed every 2 days and assayed for relaxin and progesterone (P) at the conclusion of each experiment.nnnSETTINGnTertiary care center.nnnPATIENTS, PARTICIPANTSnLuteinized human GC were obtained from women undergoing controlled ovarian hyperstimulation for IVF with one of the following regimens: (1) clomiphene citrate with human menopausal gonadotropins (hMG); (2) hMG alone; or (3) hMG with leuprolide acetate. All women were less than 40 years of age, in good health, and were not taking medications other than those used in the ovulation-induction regimen.nnnMAIN OUTCOME MEASURESnLevels of P and relaxin in spent media.nnnRESULTSnRelaxin secretion by luteinized human GC was dependent on hCG stimulation and was detected only after a time lag in culture. After relaxin secretion was detected, it was maintained throughout the culture period (10 to 22 days). Luteinized human GC produced P immediately under both basal and stimulated conditions. Progesterone production continued throughout the culture period with hCG-stimulated cells producing significantly greater P after 4 to 8 days in culture.nnnCONCLUSIONSnLuteinized human GC obtained at the time of oocyte retrieval secrete relaxin in response to hCG stimulation and secrete P under both basal and hCG-stimulated conditions, thereby serving as a model to explore luteal function and control.

Follicular development and oocyte maturation after stimulation with gonadotropins versus leuprolide acetate/gonadotropins during in vitro fertilization.

Follicular development and oocyte maturation were compared in 22 patients stimulated with human menopausal gonadotropins/human chorionic gonadotropin (hCG, group I) and in 52 women also treated with the gonadotropin-releasing hormone agonist (GnRH-a) leuprolide acetate (LA, group II). Suppression of endogenous leutinizing hormone (LH) surges by LA allowed delayed hCG administration, resulting in higher peripheral estradiol levels, more retrieved oocyte cumulus corona complexes, and greater numbers of cryopreserved embryos. Reduction in spontaneous LH surges in the GnRH-a cycles may have allowed time for larger follicular fluid (FF) volume accumulation during all phases of oocyte cumulus corona complex maturation, restoring synchrony between FF volume and oocyte cumulus corona complex maturity.

Pregnancy after an unsuccessful oocyte donation cycle

Clearly, to provide adequate counseling to women with POF, information is critically needed concerning the background incidence of spontaneous improvement in ovarian function as well as carefully designed, controlled studies to evaluate the efficacy of presumed therapeutic intervention. The case presented herein underscores our lack of adequate information about this common reproductive disorder.

Peripheral relaxin levels during pregnancy in a woman with homozygous familial hypobetalipoproteinemia

A case of a normal pregnancy conceived spontaneously in a 22-year-old woman with hypobetalipoproteinemia evidenced peripheral levels of relaxin in the range of uncomplicated singleton pregnancies in conjunction with low peripheral levels of progesterone. The establishment and maintenance of uterine quiescence in this hypoprogestational pregnancy may be attributable to these normal relaxin concentrations or to local uterine factors, including decidual relaxin production, which would not be reflected in circulating relaxin levels.

Detection of premature luteinization with serum progesterone levels at the time of the postcoital test

Poor cervical mucus (CM) may be caused by a number of factors, including premature luteinization, local cervical effects, and inadequate folliculogenesis. In an attempt to distinguish between these causes of poor CM, we obtained progesterone (P) levels at the time of postcoital tests (PCTs) in infertile women during spontaneous or clomiphene citrate (CC)-stimulated cycles. The amount of CM, viscosity, ferning, spinnbarkeit, and cellularity were each scored from 0 to 3 points on the day after detection of the urinary luteinizing hormone surge (luteal day 1). The charts of 46 such patients were retrospectively reviewed. Eleven control patients with good CM scores (>10) had low P levels ( 2.5ng/mL. Overall, 94.4% of CC-stimulated cycles versus 64.3% of spontaneous cycles had abnormal CM scores (

Poor in vitro fertilization outcome with semen yielding low sperm density ‘swim-ups’ is not because of altered sperm motion parameters

was used to measure P-induced Ca2+ influx. Progesteroneinduced acrosome reaction was monitored after acrosomal staining with Pisum sativum agglutinin. Results: Among 8 patient sperm samples with normal spermiogram values (of 53 examined), 5 showed a reduced percentage of P-binding spermatozoa and an abnormal response to the hormone in terms of Caz+ influx and the acrosome reaction. Conclusions: Defective function of a sperm surface P receptor is described in some cases of male infertility. The observed fluorescence microscopic patterns of hormone binding may be used to further investigate receptor activity in unexplained male infertility.

Poor in vitro fertilization outcome with semen yielding low sperm density “swim-ups” is not because of altered sperm motion parameters**Presented at the 46th Annual Meeting of The American Fertility Society, Washington, D.C., October 13 to 18, 1990.

OBJECTIVEnTo examine fertilization, cleavage, and pregnancy rates (PRs) with semen samples yielding numbers of total motile sperm per swim-up ranging from < 1 to > 20 x 10(6) and to correlate the findings with changes, if any, in the sperm motion parameters.nnnDESIGNnFertilization, cleavage, and pregnancy outcomes in 439 in vitro fertilization (IVF) cycles were correlated with the total number of motile sperm per swim-up and the sperm motion parameters as determined with an automated semen analyzer.nnnSETTINGnA university-based tertiary referral hospital center.nnnPATIENTSnPatients undergoing IVF or intrauterine insemination treatments for multiple etiologies.nnnRESULTSnHigher numbers of motile sperm per swim-up, most notably above the value of 3 x 10(6) motile sperm, were associated with improved fertilization rates and viable PRs. Sperm velocity, linearity, amplitude of lateral head displacement, and flagellar beat per cross frequency for sperm from swim-ups with poor or good pregnancy outcome, however, showed no significant differences.nnnCONCLUSIONSnAs a group, semen samples that yield < or = 3 x 10(6) motile sperm per swim-up are associated with poor fertilization rates, cleavage rates, and PRs. This relationship can not be attributed to differences in sperm motion parameters.

Transfer of cryopreserved-thawed embryos: The natural cycle versus controlled preparation of the endometrium with gonadotropin-releasing hormone agonist and exogenous estradiol and progesterone (GEEP)

Modeled on our successful experience with oocyte donation, we present a novel, viable approach to cryopreserved-thawed embryo transfers (ETs) in women with recalcitrant ovarian dysfunction: gonadotropin-releasing hormone agonist and exogenous estradiol and progesterone (GEEP). After attainment of ovarian suppression, seven such women received physiological steroidal replacement regimens with cryopreserved-thawed ETs prospectively synchronized with the 4th day of progesterone administration and two conceived. These GEEP cycles and cryopreserved-thawed ETs were prospectively compared with cryopreserved-thawed ETs performed on the 4th day of exposure to progesterone in 20 spontaneous cycles and in 5 oocyte donation-steroidal replacement cycles. Pregnancies occurred after three cryopreserved-thawed ETs in each of these groups. We conclude that GEEP constitutes a successful preparation for cryopreserved-thawed ETs, at the least, in women with ovulatory dysfunction.