Effects of functional ovarian cysts detected on the 7th day of gonadotropin-releasing hormone analog administration on the outcome of IVF treatment

OBJECTIVE: To investigate the impact of functional ovarian cysts on the time required to achieve pituitary suppression, follicular development, embryo quality, and pregnancy rates during IVF treatment. DESIGN: Prospective observational study. INTERVENTION(S): Daily treatment with buserelin (sc 500 microg) was initiated on day 2 of menstruation. Ultrasound and hormonal tests were performed on days 1, 7, 11, 14, and weekly thereafter until pituitary suppression was achieved. RESULT(S): 48 patients underwent 51 cycles of IVF treatment. A functional cyst was detected in three cycles (5.8%) with baseline ultrasound scan and in 27 cycles (52.9%) on day 7 of buserelin administration. Patients who developed a cyst required a significantly longer time to achieve pituitary suppression (21 vs. 7 days), had a significantly lower FSH level at the time of initiation of gonadotropins, required more ampules of gonadotropin (45 vs. 41 ampules), developed less follicles (13 vs. 17.5), and had lower embryo quality. However, there were no differences in the implantation (23.5% vs. 17.2%) and pregnancy rates (37.2% vs. 29.2%) between two groups. CONCLUSION(S): Functional cysts prolong the period to achieving pituitary suppression, increase gonadotropin requirements, and decrease follicular recruitment and embryo quality. They have, however, no negative effect on pregnancy rates.     

The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization.

OBJECTIVE: To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle. DESIGN: Prospective randomized study. PATIENTS: Ninety-one patients having their first attempt at IVF. INTERVENTIONS: Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle. RESULTS: The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2. CONCLUSIONS: The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF.     

Microdose follicular phase gonadotropin-releasing hormone agonists (GnRH-a) compared with luteal phase GnRH-a for ovarian stimulation at in vitro fertilization

Objective: To compare an ovarian stimulation protocol using microdose follicular phase GnRH agonist (GnRH-a) and oral contraceptive (OC) pills to a luteal phase GnRH-a protocol.

Design: Retrospective analysis.

Setting: University affiliated IVF program.

Patient(s): One hundred seventy patients who underwent IVF and ET in 1996.

Intervention(s): Patients were assigned to either a midluteal start of leuprolide acetate (LA) 1 mg/d, reduced to 0.5 mg/d after addition of gonadotropins (LUT), or OC pills until cycle day 0 followed by 20 μg of LA every 12 hours on cycle day 3 with addition of gonadotropins on cycle day 5 (MICRO).

Main Outcome Measure(s): Number of FSH ampules, days of stimulation, peak E₂, and number of oocytes retrieved.

Result(s): There were no statistically significant differences in the main outcome measures between the two groups using an age-matched ANOVA. Clinical pregnancy rate per cycle start was not statistically different (LUT = 54%, and MICRO = 37%). The cancellation rate was significantly higher in the MICRO group (22.5% vs. 8.2%).

Conclusion(s): Given the higher cancellation rate in the microdose group, a randomized clinical trial is required to determine the possible benefit of a lower dose of GnRH-a in patients with normal ovarian function.     

Chronic suppression of testicular function by constant infusion of gonadotropin-releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata).

OBJECTIVE: To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata). ANIMALS: Proven fertile male monkeys exhibiting normal testicular function. PROTOCOL: Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50 micrograms buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored. RESULTS: (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility. CONCLUSION: Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T.     

Congenital bilateral absence of the vas deferens: clinical characteristics, biological parameters, cystic fibrosis transmembrane conductance regulator gene mutations, and implications for genetic counseling

Objective: To evaluate relationships between the phenotypic and genotypic characteristics of patients with congenital bilateral absence of the vas deferens (CBAVD).

Design: Retrospective study.

Setting: A university hospital urology–andrology department.

Patient(s): Forty-one men with CBAVD.

Intervention(s): CBAVD was diagnosed during surgical and/or ultrasound exploration of the vasa deferentia (VD) (n = 39), or on the basis of impalpable scrotal VD (n = 2).

Main Outcome Measure(s): History, clinical and seminal characteristics, and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations including IVS-8 polyT analysis.

Result(s): A palpable scrotal vas deferens was present as a fibrous cord or nonpermeable duct in 13% of patients undergoing surgical exploration. Seminal vesicles were bilaterally absent in 28% of patients. No CFTR gene mutation or 5T allele was detected in 24.5% of the patients. Two CBAVD patients with renal agenesis carried a CFTR gene mutation (ΔF508/5T–9T and R117G/7T–9T). CBAVD patients who have both a semen volume of ≤1.0 mL and a semen pH of <7.0 have a significantly higher risk of severe CFTR gene mutation (OR = 9.12 [95% CI = 1.81–49.50]).

Conclusion(s): A palpable scrotal vas deferens was found in 13% of CBAVD patients. Semen volume of ≤1.0 mL and semen pH of <7.0 in CBAVD patients were associated with a higher risk of severe CFTR gene mutations. Patients with CBAVD and renal agenesis should be screened for CFTR gene mutations before assisted reproductive techniques are used.     

Inhibin B response to EFORT is associated with the outcome of oocyte retrieval in the subsequent in vitro fertilization cycle

Objective: To examine whether the magnitude of the rise in inhibin B levels after gonadotropin challenge is associated with subsequent response to ovarian stimulation during IVF.

Design: Inhibin B serum levels after EFORT (exogenous follicle-stimulating hormone ovarian reserve test).

Setting: Academic clinical practice.

Patient(s): Serum samples from women who had undergone ovarian reserve screening with FSH in preparation for IVF. Thirteen of these women had a poor response in IVF (canceled cycle for low estradiol and/or no oocytes retrieved), and 19 had a good response (≥10 oocytes retrieved).

Intervention(s): EFORT test.

Main Outcome Measure(s): Baseline (day 3) serum E₂ (bE₂), FSH (bFSH), and inhibin B (bInhB) levels and inhibin B and E₂ levels 24 hours after EFORT (ΔInhB and ΔE₂).

Result(s): The mean bInhB and ΔInhB levels were significantly higher in good vs. poor responders. The odds ratio of having a good response for women with a ΔInhB of 202 pg/mL was 51.8 times (95% CI = 6.1–1,244) the corresponding odds for women with a ΔInhB of 49 pg/mL. As expected, ΔE₂ was also significantly higher in good vs. poor responders; however, combination of ΔE₂ plus ΔInhB did not improve the odds for predicting IVF response.

Conclusion(s): Our data suggest that ΔInhB after EFORT may provide a method for predicting ovarian response to hyperstimulation in a subsequent IVF cycle.     

Pretreatment with an Oral Contraceptive Is Effective in Reducing the Incidence of Functional Ovarian Cyst Formation During Pituitary Suppression by Gonadotropin-Releasing Hormone Analogues

Purpose: Our purpose was to assess the effect of pretreatment with oral contraceptives (OCs) on the formation of functional ovarian cysts during pituitary supression with gonadotropin-releasing hormone (GnRH) agonists, subsequent follicular development, and pregnancy rates. Methods: A retrospective case-controlled study of 31 in vitro fertilization (IVF) patients, all of whom in a previous cycle had commenced the long protocol of GnRH-agonist (Buserelin) in the early follicular phase and were pretreated in a subsequent cycle with 2 weeks of an OC containing 30 g of ethinyl estradiol and 150 g of desogestrel prior to GnRH-agonist administration, was undertaken. Follow-up visits were arranged after a minimum of 11 days of GnRH-agonist administration and weekly thereafter until pituitary suppresion was achieved. Results: Cysts were detected in 16 (51.6%) of the 31 patients not pretreated with OCs, and in 0 (0%) of the 31 patients pretreated with OCs (odds ratio = 67.1; 95% confidence interval = 5.6–350.7). Patients pretreated with OCs achieved pituitary suppression more rapidly (median difference = 4 days; 95% confidence interval = 2–7) and had comparable gonadotropin requirements and pregnancy rates. Conclusions: Pretreatment with OCs prior to pituitary suppression in the early follicular phase decreases ovarian cyst formation, without an apparent effect on subsequent follicular recruitment or pregnancy rates.     

Failure of the combination of sequential oral and transdermal estradiol plus norethisterone acetate to affect plasma homocysteine levels

Objective: A high level of plasma homocysteine may be deleterious to vascular health. We therefore compared the effect of combinations of sequential oral and transdermal estradiol plus norethisterone acetate on plasma homocysteine.

Design: Prospective, randomized study.

Setting: Outpatient department of obstetrics and gynecology in a university hospital.

Patient(s): Forty-two healthy, nonsmoking postmenopausal women starting hormone replacement therapy (HRT) to control climacteric symptoms.

Intervention(s): In a randomized order, the women started using either oral HRT (2 mg of estradiol on days 1–12, 2 mg of estradiol plus 1 mg of norethisterone acetate (NETA) on days 13–22, and 1mg of estradiol on days 23–28; N = 21) or transdermal HRT (50 μg/d of estradiol on days 1–28 and 250 μg/d of norethisterone acetate on days 15–28, N = 21) for 1 year.

Main Outcome Measure(s): Fasting plasma levels of homocysteine were measured before the treatment and during the combined estradiol-plus-NETA phases of the sixth and 12th treatment cycles.

Result(s): Basal homocysteine levels in the oral group (8.2 ± 3.1 μmol/L, mean plusmn;SD) and transdermal group (8.7 plusmn; 1.8 μmol/L, mean plusmn;SD) were not affected by the estradiol-plus-NETA combination.

Conclusion(s): Neither an oral nor a transdermal combination of sequential estradiol and NETA causes significant changes in plasma homocysteine in Finnish postmenopausal women with normal baseline homocysteine levels.     

Recombinant or urinary follicle-stimulating hormone? A cost-effectiveness analysis derived by particularizing the number needed to treat from a published meta-analysis

Objective: To demonstrate that particularizing pooled results of a meta-analysis can derive incremental cost effectiveness of superovulation with recombinant follicle-stimulating hormones (rFSH) vs. the highly purified urinary form (uFSH) for assisted conception.

Design: A retrospective study.

Setting: An assisted conception unit in the United Kingdom.

Patient(s): One hundred forty-five fresh in vitro fertilization (IVF) and 58 fresh intracytoplasmic sperm injection (ICSI) cycles.

Intervention(s): rFSH vs. uFSH.

Main Outcome Measure(s): Incremental cost-effectiveness (i.e., cost needed to treat, or CNT) and budget-impact analyses of rFSH vs. uFSH.

Result(s): In women less than 30 years old, the clinical pregnancy rate was 37.7% (95% CI 24.8%–52.1%), the particularized number needed to treat (pNNT) was −19, and the cost needed to treat was £5070.51 (£3660.53 to £7619.32). For the 30- to 35-year-old age group, the clinical pregnancy rate was 29.9% (95% CI 20.0%–41.4%), the particularized number needed to treat was −24, and CNT was £7335.59 (£5284.11 to £10,941.22). For the 36- to 40-year-old age group, the clinical pregnancy rate was 30.6.0% (95% CI 19.6%–43.7%), the particularized number needed to treat was −23.0, and the CNT was £8569.67 (£5998.70 to £13,413.24).

Conclusion(s): The CNT and thus the budget impact analyses (the extra number of cycles that can be funded by the CNT) both increase directly with age of the patient, and inversely with the clinical pregnancy rate.     

The significance of delayed suppression using buserelin acetate and recombinant follicle-stimulating hormone in a long protocol in vitro fertilization program

OBJECTIVE: To determine whether the time taken to achieve ovarian suppression has an impact on ovarian responsiveness and the outcome of IVF-ET. DESIGN: Retrospective analysis. SETTING: An assisted reproduction unit at a university center. PATIENT(S): Patients undergoing a long protocol of IVF-ET that included buserelin acetate therapy initiated on day 2 of the cycle and recombinant FSH. INTERVENTION(S): Patients were divided into two groups according to the duration of buserelin acetate therapy required to achieve pituitary and ovarian suppression (group 1 = 2 weeks, n = 172; group 2 = > or =3 weeks, n = 337). MAIN OUTCOME MEASURE(S): Number of recombinant FSH ampules administered, duration of ovarian stimulation (days), ovarian response, and IVF outcome. RESULT(S): The patients in group 2 had lower mean E2 levels after 5 days and 9 days of stimulation than the patients in group 1. The number of recombinant FSH ampules administered and the number of days of stimulation required were higher in group 2 than in group 1. These differences were prominent in the subgroups of older patients (> or =36 years) and patients who had no evidence of polycystic ovaries on ultrasound examination. The number of oocytes retrieved and fertilized, the cancelation rate, and the pregnancy rate were similar in the two groups. CONCLUSION(S): Prolonged administration of a GnRH agonist to achieve suppression leads to a reduced ovarian response, particularly in women > or =36 years of age, but does not affect the success rate of IVF-ET.     

Risk factors at caesarean section and failure of subsequent trial of labour

Objective: To identify risk factors at caesarean section (CS), related to failure of a trial of labour (TOL) in subsequent pregnancy. Study design: Hospital records (1988–1999) of the index pregnancy were reviewed at caesarean delivery for oxytocine use, indication for caesarean, dilatation of cervix, speed of dilatation, duration of contractions and birth weight. The records of the subsequent pregnancy were reviewed for successful vaginal birth after caesarean (VBAC), maternal and neonatal outcome. Data were tested for statistical significance with a Mantel–Haenszel equation for odds ratios (OR, with 95% confidence interval (CI)), a Fisher exact test or a Student’s ‘t’-test. Results: From 214 women with a previous caesarean section, 68.7% underwent a TOL, which was successful in 71.4%. A labour pattern during the index pregnancy characterised by oxytocine use (OR=3.1; 95% CI=1.4–7.1), contractions for more than 12 h (OR=3.0; 95% CI=1.3–7.0) and cervical dilatation less than 1 cm/h (OR=5.6; 95% CI=1.1–39.4) increased the risk of a failed TOL at subsequent labour significantly. Conclusion: Women who attempt VBAC may be informed that a labour pattern of their index pregnancy characterised by oxytocine use, contractions for more than 12 h and slow dilatation is associated with a reduced chance of success. A partograph obtained during first labour can be a managerial tool for subsequent labour.     

Inflammatory bowel disease and preterm delivery

Objective: The present study investigates pregnancy outcome in women with IBD and examines the effect of pregnancy on the severity of IBD. Method: A case-control study comparing deliveries by mothers with IBD between January 1988 and January 2005 was performed. For every birth by a mother with IBD, four births by non-IBD mothers were randomly selected and adjusted for ethnicity and year of delivery. Result: During the study period there were 48 deliveries to patients with Crohn's disease and 79 deliveries to patients with ulcerative colitis. Higher rates of preterm delivery (< 37 weeks) were found among patients with IBD as compared to the controls (odds ratios (OR) = 2.2; 95% confidence interval (CI) = 1.3–3.8). This association remained significant after adjustment for labor induction and multiple gestations, using the Mantel–Haenszel technique (weighted OR = 2.1; 95% CI 1.3–3.5 and weighted OR = 2.0; 95% CI 1.2–3.5; P = 0.012; respectively). In addition, these patients had higher rates of fertility treatments (OR = 2.2; 95% CI = 1.1–4.4). Using a multivariate analysis, controlling for maternal age and fertility treatments, preterm delivery was seen to be significantly associated with IBD (adjusted OR = 2.0; 95% CI = 1.2–3.5). Perinatal outcomes, such as perinatal mortality, low Apgar scores, and congenital malformations, were comparable to the outcomes in the control group. Conclusion: Maternal IBD is an independent risk factor for preterm delivery. IBD is not associated with adverse perinatal outcome.     

Pharmacokinetics and pharmacodynamics of single-chain recombinant human follicle-stimulating hormone containing the human chorionic gonadotropin carboxyterminal peptide in the rhesus monkey

Objective: To compare the pharmacokinetics of a long-acting FSH analog containing the hCG-β carboxyterminal peptide (recombinant hFSH–CTP) with native recombinant hFSH and describe the pharmacodynamics of recombinant hFSH–CTP after SC injection in female rhesus monkeys.

Design: Rhesus monkey study.

Setting: Academic research environment.

Animal(s): Ten female rhesus monkeys.

Intervention(s): Recombinant hFSH and recombinant hFSH–CTP were administered via a single SC or IV dose to rhesus monkeys, and serial phlebotomy was performed (n = 2 and N = 4 for SC recombinant hFSH and recombinant hFSH–CTP, respectively; for IV dosing, N = 1 in each group). An additional two monkeys were pretreated with SC ganirelix and received SC recombinant hFSH–CTP after confirmation of pituitary suppression.

Main Outcome Measure(s): Plasma disappearance rate of recombinant hFSH and recombinant hFSH–CTP and serum estradiol levels.

Result(s): The elimination half-life of recombinant hFSH–CTP was twofold and fourfold longer than that for recombinant hFSH after SC and IV dosing, respectively. The absorption half-life was approximately threefold longer for recombinant hFSH–CTP than for recombinant hFSH after SC administration. Recombinant hFSH–CTP stimulates estradiol secretion for 5–7 days after an isolated SC dose.

Conclusion(s): Addition of the hCG-β carboxyterminal peptide to hFSH-β results in an FSH analog with longer absorption and elimination half-lives compared with native hormone. This analog is capable of prolonged ovarian stimulation in rhesus monkeys after an isolated SC injection.     

Acute Changes in Endometrial Thickness After Aspiration of Functional Ovarian Cysts

Objective: To evaluate the influence of aspiration of functional ovarian cysts on endometrial thickness.

Design: Prospective study.

Setting: An IVF Unit of an academic medical center.

Patient(s): Twenty-two patients from our IVF program, in whom administration of a gonadotropin-releasing hormone agonist preparation in the “long protocol” failed to induce pituitary desensitization, as evidenced by a serum E₂ concentration of >55 pg/mL and the presence of an ovarian cyst of >20 mm in diameter.

Intervention(s): Transvaginal ultrasonographic-guided cyst aspiration was performed, and 2 days later, serum E₂ concentration and endometrial thickness were reassessed.

Main Outcome Measure(s): The values of serum E₂ concentration and endometrial thickness before and after cyst aspiration were compared.

Result(s): Two days after ovarian cyst aspiration, the serum E₂ concentration dropped from a mean (±SD) of 203 ± 93 to 37 ± 34 pg/mL. The mean (±SD) endometrial thickness was 9.6 ± 2.0 mm before cyst aspiration and decreased to 5.9 ± 2.4 mm after the procedure.

Conclusion(s): Within 48 hours after ovarian cyst aspiration, a significant reduction in endometrial thickness occurs concomitant with a sharp decline in serum E₂ levels. The phenomenon of acute reduction in endometrial thickness in response to acute estrogen withdrawal has not been described previously. The exact mechanism and endometrial component involved in the “shrinking” process should be further investigated.     

Oral contraceptives,tubal sterilization,and functional ovarian cyst risk

OBJECTIVE: To determine whether current contraceptive method affects functional ovarian cyst risk, with emphasis on oral contraceptives (OCs) and tubal sterilization. METHODS: We conducted a case-control study of 18-39-year-old health maintenance organization enrollees with a functional ovarian cyst diagnosed between January 1, and June 30, 1994, and age-matched female controls randomly selected from enrollment files. In-person interviews as well as medical and pharmacy records were obtained for 78% of cases and 82% of controls; these analyses were based on 392 cases and 623 controls. Odds ratios (ORs) calculated with unconditional logistic regression were used to estimate the risk of a functional ovarian cyst diagnosis associated with current contraceptive method. RESULTS: In multivariable analyses adjusting for age, education, number of live births, and reference year, the overall OR was 0.72 (95% confidence interval [CI] 0.53, 0.99) for current OC use, compared with use of nonsurgical nonhormonal contraception or no contraception. The risk associated with use of 35 microg ethinyl estradiol monophasic OCs (OR 0.69; 95% CI 0.44, 1.10) was slightly lower than that associated with less than 35 microg ethinyl estradiol monophasic (OR 0.79; 95% CI 0.43, 1.47) or multiphasic OCs (OR 0.76; 95% CI 0.49, 1.19). Women with tubal sterilization had a substantially increased risk of a functional ovarian cyst diagnosis (OR 1.70; 95% CI 1.05, 2.75) compared with women using nonhormonal or no contraception. CONCLUSION: Our findings suggest that low-dose OC use has little or no effect on functional ovarian cyst likelihood. The increased risks we found associated with tubal sterilization merit further investigation.     

Fecundity of Infertile Women with Minimal or Mild Endometriosis And Women with Unexplained Infertility

Objective: To assess whether infertile women with minimal or mild endometriosis have lower fecundity than women with unexplained infertility.

Design: Prospective cohort study.

Setting: Twenty-three infertility clinics across Canada.

Patient(s): Three hundred thirty-one infertile women aged 20–39 years.

Intervention(s): Diagnostic laparoscopy for infertility. Infertile women with minimal or mild endometriosis (n = 168) were compared with women with unexplained infertility (n = 263). Both groups were managed expectantly. The women were followed up for 36 weeks after the laparoscopy or, for those who became pregnant, for up to 20 weeks of the pregnancy.

Main Outcome Measure(s): Fecundity refers to the probability of becoming pregnant in the first 36 weeks after laparoscopy and carrying the pregnancy for ≥20 weeks. The fecundity rate is the number of pregnancies per 100 person-months.

Result(s): Fecundity was 18.2% in infertile women with minimal or mild endometriosis and 23.7% in women without endometriosis (log-rank test). The fecundity rate was 2.52 per 100 person-months in women with endometriosis and 3.48 per 100 person-months in women with unexplained infertility. The crude and adjusted fecundity rate ratios were 0.72 and 0.83 (95% confidence interval = 0.53–1.32), respectively.

Conclusion(s): The fecundity of infertile women with minimal or mild endometriosis is not significantly lower than that of women with unexplained infertility.     

Prospective randomized trial of the effect of two flushing media on oocyte collection and fertilization rates after in vitro fertilization

Objective: To assess the value of heparinized saline as a flushing medium for oocyte recovery.

Design: Prospective randomized study.

Setting: Academic tertiary referral center for fertility treatment.

Patient(s): Thirty-five patients, with both ovaries intact having IVF-ET.

Intervention(s): Patients were randomized either to have the follicles of the left or right ovary flushed with heparinized normal saline at the time of oocyte recovery for IVF-ET. The contralateral ovary was flushed with heparinized culture medium. Oocytes obtained from each side were cultured separately and assessed for fertilization 18–21 hours after insemination.

Main Outcome Measure(s): Collection and fertilization rates.

Result(s): A total of 481 follicles were aspirated yielding 366 oocytes. Of these, 240 fertilized. From the side flushed with saline 185 oocytes were collected from 237 follicles, which was not significantly different from 181 oocytes collected from 244 follicles on the side flushed with culture medium (odds RATIO = 1.23; 95% confidence INTERVAL = 0.79−1.92). Similarly, there was no significant difference observed in fertilization rates between oocytes obtained after saline (median 71.4%) and culture medium flush (median 75.0%) (odds RATIO = 1.08; 95% confidence INTERVAL = 0.68−1.72).

Conclusion(s): Heparinized normal saline is an equally good but cheaper and more convenient medium than standard heparinized culture medium and could replace it for flushing follicles during oocyte recovery for IVF-ET procedures.     

Vascular endothelial growth factor, nitric oxide, and leptin follicular fluid levels correlate negatively with embryo quality in IVF patients

Objective(s): To measure vascular endothelial growth factor (VEGF), nitric oxide (NO) and leptin levels in individual ovarian follicles and to examine their relationships with perifollicular blood flow, follicular metabolic indices, and the developmental potential of the corresponding oocyte and embryo.

Design: Prospective study.

Setting: Academic, tertiary care institution.

Patient(s): Unselected IVF patients.

Intervention(s): Color-pulsed Doppler analysis of perifollicular blood flow; determination of partial pressure of oxygen (pO₂), partial pressure of carbon dioxide (pCO₂), and pH and VEGF, leptin and NO levels in follicular fluid.

Main Outcome Measure(s): Fertilization and day 3 embryo morphology and cleavage.

Result(s): Fifty-five follicular fluid samples from 16 patients were studied. Mean follicular fluid levels were as follows: VEGF, 1,046 ± 863.7 pg/mL (range, <63–3,332.7 pg/mL); NO₃/NO₂, 34.2 ± 12 μM (range, 16.4–76.1 μM); and leptin, 20.1 ± 12.1 ng/mL (range, 3.3–52.2 ng/mL). Vascular endothelial growth factor had a negative correlation with embryo morphology (r = −0.28, P=.01). Leptin demonstrated a negative correlation with follicular pO₂ (r = −0.42, P=.005) and a positive correlation with follicular pCO₂ (r = 0.36, P=.02). Follicular leptin levels correlated positively with VEGF levels (r = 0.46, P=.008) and with NO₃/NO₂ levels (r = 0.39, P=.006).

Conclusion(s): Vascular endothelial growth factor, NO and leptin appear to be markers of follicular hypoxia and suboptimal embryo development. Whether fluctuations of these regulatory factors determine or reflect changes in the follicular microenvironment affecting oocyte developmental potential remains to be elucidated.     

Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: a randomized controlled trial

OBJECTIVE: To compare the efficacy of multidose medroxyprogesterone acetate and a multidose monophasic combined oral contraceptive (OC) for hemodynamically stable women with nongestational, acute uterine bleeding. METHODS: Hemodynamically stable patients with acute uterine bleeding sufficient to justify immediate medical or surgical intervention were enrolled in an open-label, randomized trial comparing oral medroxyprogesterone acetate 20 mg and a monophasic combination OC containing 1 mg norethindrone and 35 mug of ethinyl estradiol, each administered three times per day. Doses were reduced after 1 week to 20 mg per day and one tablet per day for the next 3 weeks for the medroxyprogesterone acetate and OC groups, respectively. Following baseline assessment, patients completed daily treatment and symptom logs collected at 14 and 28 days after initiation of therapy. RESULTS: Forty patients were randomly assigned, 20 in each group; 33 were evaluated at the 14-day visit. Emergency surgical procedures were avoided in 100% of those women taking medroxyprogesterone acetate and 95% of the OC group. Cessation of bleeding had occurred in 88% of the OC group and 76% of those receiving medroxyprogesterone acetate, with a median time to bleeding cessation of 3 days for both groups. Compliance with therapy was higher in the medroxyprogesterone acetate group than the OC group, but there was no overall difference in the incidence of treatment-related nausea and bloating. CONCLUSION: This randomized trial is limited by sample size but suggests that both regimens may be effective and reasonably well tolerated. CLINICAL TRIAL REGISTRATION: Current Clinical Trials (clinicaltrials.gov, www.clinicaltrials.gov) Identifier: NCT00350480 LEVEL OF EVIDENCE: II-1.     

Pregnancy-associated plasma protein-A polymorphism and the risk of recurrent pregnancy loss

Pregnancy-associated plasma protein-A (PAPP-A)/insulin-like growth factor-binding protein-4 (IGFBP4) protease is a member of the metzincin family of metalloproteases, known as a sensitive biomarker of adverse pregnancy outcomes. Recently, a missense A/C (Tyr/Ser) polymorphism (dbSNP: rs7020782) in the PAPPA gene has been reported. To examine the association between recurrent pregnancy loss (RPL) and this polymorphism, a case-control study of 215 cases with two or more pregnancy losses (PLs) and 420 fertile controls was performed. Genotyping of the PAPPA polymorphism was determined by allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Sixty-nine cases (32.1%) were heterozygous and 11 cases (5.1%) were homozygous for the C allele of PAPPA; the respective figures were 127 (30.2%) and 11 (2.6%) in the controls. Women carrying the C allele had a tendency to increased risk of RPL (AA genotype [reference]; AC genotype: odds ratio [OR], 1.17; 95% confidence interval [CI], 0.82–1.68; CC genotype: OR, 2.06; 95% CI, 0.87–4.90), but it was not significant. Women with three or more PLs had a similar tendency (AA genotype [reference]; AC genotype: OR, 1.04; 95% CI, 0.66–1.64; CC genotype: OR, 2.20; 95% CI, 0.82–5.91). The risk of RPL with at least one PL after 9 weeks’ gestation significantly increased in women carrying the C allele (AA genotype [reference]; AC genotype: OR, 1.54; 95% CI, 0.95–2.49; CC genotype: OR, 2.83; 95% CI, 1.00–8.05; AC + CC genotypes: OR, 1.65; CI, 1.04–2.62). This is the first report on the PAPPA gene polymorphism in women with RPL, demonstrating some association between the investigated polymorphism and the risk of RPL.