Pharmacokinetics of meropenem in critically ill patients with acute renal failure treated by continuous hemodiafiltration

A prospective, randomized, double-blind and placebo-controlled study was conducted to assess the effectiveness of i.v. administration of 6% hydroxyethyle starch solution (HES) in preventing moderate and severe ovarian hyperstimulation syndrome (OHSS) in patients in an in-vitro fertilization programme. A total of 101 women who had serum oestradiol concentrations >1500 pg/ml and/or more than 10 follicles on day of human chorionic gonadotrophin (HCG) administration were recruited into two groups: HES group (n = 51) received 1000 ml 6% HES; and the placebo group (n = 50) received 1000 ml of sodium chloride 0.9% solution at the time shortly after embryo transfer. Follow-up examinations 7 +/- 1 and 14 +/- 1 days after embryo transfer included transvaginal ultrasound (diameters of each ovary and maximum cysts, number of cysts, ascites), blood tests (serum oestradiol, progesterone, beta-HCG, C-reactive protein, blood count, plasma proteins, electrolytes, kidney function tests) and evaluation of abdominal pain, nausea, diarrhoea, abdominal swelling and weight gain. Only one moderate OHSS developed in the HES group whereas seven moderate-severe cases were observed in the placebo group (P = 0.031). Furthermore, serum oestradiol concentration, leukocyte count, increase in abdominal circumference and weight gain 14 days after embryo transfer were significantly higher in the placebo group. There were no differences between the two groups in terms of age, oestradiol concentration and number of follicles at time of HCG injection. Administration of 6% HES prevents the development of moderate-severe OHSS in risk patients.     

Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post-retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved-thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.     

A prospective study of early pregnancy loss

The New York State Early Pregnancy Detection Study was a prospective study of early pregnancy loss, between implantation and menses, in 217 women attempting to become pregnant during 1989-1992. Women collected urine samples on three consecutive mornings during the late luteal phase of their menstrual cycle, for up to 12 cycles, contributing samples for 1253 menstrual cycles. Urinary human chorionic gonadotrophin (HCG), measured using an immunoradiometric assay, was the biomarker for pregnancy. We observed a range of early pregnancy loss (EPL) rates, from a low estimate of 11.0% to a high estimate of 26.9%, depending on the definition used and the subgroup analysed. Based on a definition of 3 days of HCG concentration > or = 4.00 pmol/l, 2 days > or = 5.33 pmol/l or the last day of HCG > or = 6.67 pmol/l, we identified 115 positive cycles; 95 cycles were clinically confirmed pregnancies and 20 cycles were EPL, giving an EPL rate of 17.4% [95% confidence interval (CI) 11.0-25.6]. In addition, we observed an EPL rate of 19.5% (95% CI 11.3-30.1) for samples collected within a 15 day window around menses, and a rate of 20.3% (95% CI 11.3-32.2) for samples limited to the first three menstrual cycles. Because studies use urine collection schemes other than daily sampling, the definition of pregnancy will be crucial in defining EPL.     

Ovarian stimulation and in vitro fertilization in women with mature cystic teratomas

OBJECTIVE: To report the results of ovulation induction and in vitro fertilization-embryo transfer (IVF-ET) in patients with ovarian cystic teratomas. METHODS: Six women with ultrasonographically diagnosed ovarian cystic teratomas (mean diameter 2.4 cm) who presented with infertility underwent IVF-ET (n = 4) or ovulation induction (n = 2). Serial ultrasound examinations were used to determine the size of the cystic teratomas during therapy and throughout pregnancy. RESULTS: Ovarian stimulation was successful, as evidenced by the serum estradiol concentration on the day of hCG administration (mean in IVF-ET patients, 3558+/-1319 pg/mL) and the number of oocytes retrieved (10+/-4.24). Three patients having IVF-ET and both patients having ovulation induction conceived, and six healthy infants were born. Cyst sizes remained unchanged throughout treatment and pregnancy. There were no cyst-related complications during ovulation induction or IVF-ET, or during the entire course of pregnancy, labor, and delivery. CONCLUSION: The presence of ovarian cystic teratoma should not be considered a contraindication for therapy in women undergoing ovulation induction and IVF-ET.     

Serum progesterone at the time of human chorionic gonadotrophin does not predict pregnancy in in-vitro fertilization and embryo transfer

Controversy exists as to whether the serum concentration of progesterone on the day of human chorionic gonadotrophin (HCG) administration following ovarian stimulation for in-vitro fertilization (IVF) and embryo transfer can be used to predict the likelihood of success. This retrospective study was undertaken to answer this question by analysing a large population of IVF and embryo transfer cycles (n = 756). In addition to the concentration of progesterone on the day of HCG administration, all variables known to impact on IVF and embryo transfer success (such as patient age), indication for IVF and embryo transfer, number of oocytes retrieved and the number of embryos generated and transferred were examined. There was a significant increase in the number of oocytes retrieved with increasing progesterone concentration at the time of HCG administration. However, there was no correlation of progesterone concentration at HCG administration with pregnancy and implantation rates. It is concluded that previous reports associating a slight elevation of progesterone in gonadotrophin-releasing hormone agonist ovarian stimulation cycles for IVF and embryo transfer may be misleading because of a small sample size or the presence of confounding variables that affect IVF and embryo transfer success.     

Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer

OBJECTIVE: To determine if an increase in plasma P occurring before hCG administration might impair the outcome of IVF-ET. DESIGN: Five hundred eighty-five IVF-ET cycles were prospectively studied for the occurrence of plasma P elevation before hCG administration. SETTING: Tertiary institution, IVF-ET program, H?pital A. Béclère. PATIENTS: Participating patients included IVF-ET candidates 23 to 42 years of age only, excluding the couples in whom a male factor was a primary or an accessory cause of infertility. MAIN OUTCOME MEASURES: To clarify the practical consequences on IVF-ET outcome of pre-hCG increases in plasma P, we studied 585 consecutive IVF-ET cycles. These were divided into two groups according to plasma P levels observed on the day of hCG administration; plasma P of 0.9 ng/mL (2.9 nmol/L) was taken as an arbitrary cutoff value. Group A included 485 IVF cycles in which plasma P was < or = 0.9 ng/mL (2.9 nmol/L); group B included the remaining 100 cycles in which plasma P was > 0.9 ng/mL (2.9 nmol/L). RESULTS: The number of mature oocytes retrieved, the oocyte cleavage rate, and the number of embryos obtained were similar in groups A and B. In contrast to this apparent similarity in oocyte quality, a decrease in pregnancy rate (PR) and a trend for a decrease in embryo implantation rate were observed in group B in comparison with group A. CONCLUSIONS: The similar fertilization and cleavage rates obtained in groups A and B suggest that pre-hCG elevation in plasma P does not lead to decreased oocyte quality. Yet the lower PR observed when plasma P rises prematurely suggests that the prolonged but discrete elevation in plasma P occurring in these cases might alter endometrium receptivity to embryo implantation.     

The relationship between ovarian vascularity and the duration of stimulation in in-vitro fertilization

The role of transvaginal pulsed colour Doppler ultrasound in the assessment of ovarian vascularity was studied in 196 in-vitro fertilization (IVF) cycles. The changes in ovarian blood flow after gonadotrophin-releasing hormone agonist (GnRHa) down-regulation and human menopausal gonadotrophin (HMG) stimulation were determined. The data obtained showed that the ovarian blood flow was significantly improved by oestradiol secretion (P = 0.05) and human chorionic gonadotrophin (HCG) administration (P = 0.003). Folliculogenesis was affected by blood flow supply. The resistance index (RI) value was significantly different (P = 0.05) according to the duration of ovarian stimulation. Patients with a mean RI value >0.56 had a longer stimulation with a significantly lower mean number of oocytes retrieved (P = 0.01) despite the administration of a standard dose of HMG. The RI value is a good indicator of modifications in ovarian vascularization during stimulation. Doppler blood flow measurement could be used to determine the optimal timing for the beginning of HMG administration in patients undergoing ovarian stimulation after down-regulation for IVF treatment.     

Pregnancy after transfer of embryos which were generated from in-vitro matured oocytes

In-vitro maturation of human oocytes is an important technique in assisted reproduction due to its potential for reducing the use of fertility drugs. We offered this technique as an alternative to cancelling the cycle to a patient who was at risk of ovarian hyperstimulation syndrome (OHSS) after treatment with gonadotrophin-releasing hormone analogue (GnRHa) and human menopausal gonadotrophin (HMG). The patient had 40 visible antral follicles with a maximum diameter of 13 mm and an oestradiol concentration of 14,000 pmol/l on cycle day 12. Immature oocytes were aspirated transvaginally under ultrasound guidance. Ten cumulus-enclosed oocytes were harvested and nine of them completed nuclear maturation to metaphase II after 48 h in culture. By 18 h after an intracytoplasmic sperm injection (ICSI) procedure, seven of these metaphase II stage oocytes displayed two distinct pronuclei and two polar bodies. All fertilized oocytes but one underwent cleaveage; four of these were transferred 2 days later. Endometrial priming was initiated with 8 mg oestradiol valerate daily from the day of oocyte retrieval and 50 mg progesterone was injected i.m. daily starting 2 days after that. A single intrauterine sac was seen containing one fetus with positive fetal heart beat on ultrasound at 7 weeks of gestation. Unfortunately, the pregnancy ended at 24 weeks shortly after premature rupture of membranes; a live healthy-looking girl was delivered who died 18 days later.     

Endometrial stripe thickness as a predictor of ectopic pregnancy

We have examined the efficacy of highly purified follicle stimulating hormone (FSH-HP) for controlled ovarian stimulation in our in-vitro fertilization (IVF) programme, and compared the results obtained with this preparation with those using human menopausal gonadotrophin (HMG) in 15 patients who had received treatment with both FSH-HP and HMG in consecutive cycles (n = 39). No differences were found in the duration of stimulation, which was 13.9 days (HMG) as compared with 14.3 days (FSH-HP). However, in the FSH-HP-treated cycles we found a striking difference in the rise of serum oestradiol, which was significantly lower than in HMG-treated cycles (2953 +/- 938 pmol/l as compared with 6349 +/- 3683 pmol/l on the day before ovum retrieval). Number and size of follicles were similar in the two groups, as were oocyte characteristics. Increase in endometrial thickness at two days prior to ovum retrieval was slightly higher after HMG. The results indicate that in combination with a long gonadotrophin-releasing hormone agonist (GnRHa) protocol, pure FSH is sufficient for adequate follicle recruitment and growth. However, since FSH-HP resulted in markedly reduced concentrations of serum oestradiol as compared to HMG cycles, IVF programmes using repeated oestradiol measurements to decide the day of ovum retrieval must take this into consideration in order not to prolong the stimulation unnecessarily.     

Hormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonist (Cetrorelix)

A third generation gonadotrophin-releasing hormone antagonist (Cetrorelix) was used during ovarian stimulation in 32 patients undergoing assisted reproduction, in order to prevent the premature luteinizing hormone (LH) surge. In all patients, ovarian stimulation was carried out with two or three ampoules of human menopausal gonadotrophin (HMG), starting on day 2 of the menstrual cycle. In addition, 0.5 mg of Cetrorelix was administered daily from day 6 of HMG treatment until the day of ovulation induction by human chorionic gonadotrophin (HCG). A significant drop in plasma LH concentration was observed within a few hours of the first administration of Cetrorelix (P < 0.005). Moreover, no LH surge was detected at any point in the treatment period in any of the 32 patients. A mean oestradiol concentration of 2111 +/- 935 ng/l was observed on the day of the HCG administration, indicating normal folliculogenesis. Like LH, progesterone concentration also dropped within a few hours of the first administration of Cetrorelix (P < 0.005). A 0.5 mg daily dose of Cetrorelix prevented a premature LH surge in all the 32 patients treated.     

Human chorionic gonadotrophin and steroid concentrations in follicular fluid: the relationship to oocyte maturity and fertilization rates in stimulated and natural in-vitro fertilization cycles

The study investigates the relationship of follicular fluid steroids and human chorionic gonadotrophin to oocyte maturity and fertilization rates in stimulated and natural cycles. Oestradiol, progesterone, testosterone and human chorionic gonadotrophin were quantified in 129 samples of follicular fluid and the progesterone:oestradiol ratio calculated. Both stimulated cycles (short and long luteinizing hormone-releasing hormone/human menopausal gonadotrophin regimens) and natural cycles were compared. A total of 60 women were studied, 20 in each group. In the natural cycles, testosterone was significantly lower in follicles with intermediate oocytes (P = 0.015). Both oestradiol and testosterone were significantly lower in stimulated cycles compared to natural cycles (P = 0.032 and P = 0.034 respectively). In the ovarian stimulation cycles, the progesterone:oestradiol ratio was significantly higher when oocytes fertilized (P = 0.052). Moreover, in the stimulated cycles, oestradiol and human chorionic gonadotrophin were singnificantly lower in the short protocol compared to the long protocol. The data demonstrate that the hormonal milieu of the follicle is altered in down-regulated stimulated cycles to varying degrees, depending partially on the type of protocol used. Furthermore, the progesterone:oestradiol ratio, rather than individual hormone concentrations, may be a useful predictor of the fertilizing capacity of the oocytes.     

Characterization of the mouse Src homology 3 domain gene Sh3d2c on Chr 7 demonstrates coexpression with huntingtin in the brain and identifies the processed pseudogene Sh3d2c-ps1 on Chr 2

OBJECTIVE: To evaluate the predictive value of the antral follicle count in patients undergoing assisted reproductive technologies (ARTs). DESIGN: Prospective study. SETTING: Tertiary care institutional hospital. PATIENT(S): Consecutively seen patients undergoing ARTs such as IVF-ET, gamete intrafallopian transfer, and tubal embryo transfer (TET). INTERVENTION(S): The ovarian antral follicle number was determined by transvaginal ultrasonography on the first or second menstrual day, before the administration of gonadotropins, in patients undergoing ARTs. MAIN OUTCOME MEASURE(S): Ovulation induction was accomplished with the use of GnRH agonist down-regulation combined with FSH and menotropin stimulation. Gamete intrafallopian transfer or TET was performed in patients with patent fallopian tubes, and IVF-ET was undertaken in the remaining patients. Analysis of variance and Mantel-Haenszel monotonic test for trends were used for data analysis. RESULT(S): A total of 149 treatment cycles for 130 couples were performed during the study period. The procedures performed included 89 ETs, 26 gamete intrafallopian transfers, 13 TET cycles, and 21 incomplete cycles (9 poor responders, 6 failed retrievals, and 6 nonfertilization cycles). All treatment cycles were divided into three groups according to the number of antral follicles (i.e., < or = 3, 4-10, and > or = 11) to evaluate the influence of various factors. The antral follicle count correlated significantly with patient age, day 3 serum FSH level, use of gonadotropins, serum estradiol concentration, number of oocytes retrieved, and, later, number of oocytes or embryos transferred. The group of patients who had a lower antral follicle count also had a significantly higher rate of cycle cancellation compared with the other two groups (68.8% vs. 5.3% and 0, respectively). No pregnancies occurred in the low antral follicle count group, whereas there was a trend toward an increasing number of pregnancies per attempt as the number of antral follicles increased (0, 23.7%, and 36.8%, respectively). CONCLUSION(S): It is easy to determine the number of antral follicles with a diameter of 2-5 mm on the first or second day of menstruation, or just before the administration of exogenous gonadotropins. We were able to predict the ovarian response and pregnancy results of patients undergoing ARTs with the use of this simple procedure.     

Involvement of ovarian kinin-kallikrein system in the pathophysiology of ovarian hyperstimulation syndrome: studies in a rat model

The purpose of the present study was to investigate a possible participation of the kinin-kallikrein system (KKS) in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Symptoms of hyperstimulation were produced in immature female rats using equine chorionic gonadotrophin followed by human chorionic gonadotrophin (HCG). At 48 h after the HCG injection, rats were injected s.c. with 100 microg/kg of HOE140, bradykinin-2 receptor antagonist. Capillary permeability was evaluated using peritoneal Evans blue dye (EB) concentrations 30 min after the i.v. injections. The EB concentrations in the hyperstimulated rats were significantly reduced 4 and 6 h after the HOE140 injection, compared with those injected with the vehicle as a control (4.58+/-0.80 versus 8.22+/-0.87 and 4.32+/-0.74 versus 8.35+/-1.03 microg respectively; P < 0.03), indicating the involvement of kinin in the pathophysiology of OHSS in this model. The administration of 10 IU aprotinin significantly reduced the peritoneal EB concentration when compared with the control (4.13+/-0.53 versus 7.95+/-1.06 microg; P < 0.01), implicating a possible role of kallikrein. Furthermore, pretreatment with RU486 (5 or 10 mg/kg) resulted in a significant reduction of ovarian kinin concentrations 48 h after the HCG injection, compared with the control (1.22+/-0.07 or 1.43+/-0.07 versus 1.94+/-0.10 pg/mg; P < 0.005 and P < 0.05 respectively). Similar results were obtained in the peritoneal EB concentrations. In addition, a significant correlation between the ovarian kinin and peritoneal EB concentrations was observed (P < 0.001, r = 0.539). Thus it was suggested that ovarian KKS plays an intermediary role in the progesterone-induced augmentation of capillary permeability in this experimental model, indicating the involvement of KKS in the pathophysiology of OHSS.     

Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection

An ultrasonographic evaluation of the endometrium was performed in 158 patients undergoing ovarian stimulation for an in-vitro assisted reproduction programme. Endometrial thickness was evaluated in 109 patients undergoing in-vitro fertilization (IVF) for female indications and in 49 patients undergoing intracytoplasmic sperm injection (ICSI) for male indications. The maximal endometrial thickness was measured on the day of human chorionic gonadotrophin (HCG) administration by longitudinal scanning of the uterus on the frozen image using electronic callipers placed at the junction of the endometrium-myometrium interface at the level of the fundus. Cases in which the endometrial thickness was >/=10 mm were included in group A; cases in which the endometrial thickness was <10 mm were assigned to group B. The age of the patients, serum 17-beta oestradiol concentrations on the day of HCG administration, the length of follicular stimulation, the number of follicles, 17-beta oestradiol concentrations per follicle on the day of HCG and the number of embryos transferred were analysed in each case. When comparing endometrial thickness and results in IVF and ICSI patients, an endometrium <10 mm predominated in IVF patients (27.5%) compared with those undergoing ICSI (16.7%) (P = 0.05); conversely an endometrium >=10 mm was more frequent in ICSI than in IVF patients. The incidence of pregnancy was higher in IVF group A patients (32/79; 41%) than in IVF group B patients (5/30; 17%) (P = 0.03), whereas no significant difference was found between ICSI group A (13/42; 31%) and ICSI group B (3/7; 43%) patients. Thus, a higher percentage of IVF patients had thin endometrium when compared with ICSI patients; thin endometrium was a prognostic indicator of pregnancy only in the case of a female indication for infertility (IVF). A thin endometrium in cases of female infertility may reflect a previous or present uterine pathology, whereas in indications of male infertility (i.e. cases using ICSI), in the absence of any associated uterine pathology, the presence of a thin endometrium is not predictive.     

Development of human primordial follicles to antral stages in SCID/hpg mice stimulated with follicle stimulating hormone

In contrast to the many detailed studies of Graafian follicles, the biology of small follicles in the human ovary is poorly understood and the trigger for follicular growth initiation remains unknown. No practical model exists to study preantral follicle growth in the human because of their slow growth rate and lack of an effective culture system. We therefore tested ovarian xenografts as a new strategy to study the early stages of ovarian follicular growth in vivo. Mice homozygous for severe combined immunodeficiency (SCID) and hypogonadism (hpg) received human ovarian xenografts under their kidney capsules. Follicle growth was assessed by morphology and proliferating cell nuclear antigen (PCNA) immunostaining. The grafts were recovered after 11 (short-term) and 17 weeks (long-term), and serially sectioned. During the last 6 weeks of long-term grafting, mice were randomized to receive either placebo or 1 IU of purified follicle stimulating hormone (FSH) s.c. on alternating days. After 11 weeks of grafting, the most advanced follicles had a maximum of two granulosa cell layers. In the absence of FSH administration, follicles did not progress beyond the two-layer stage even after 17 weeks of grafting, and the oestradiol levels remained undetectable. In the FSH-treated long-term grafts, follicles had grown to antral stages and resulted in oestradiol levels as high as 2070 pmol/l. Growth initiation indices did not differ between control and FSH-treated grafts. This study demonstrates that follicles can survive and grow in human ovarian tissue grafted under the renal capsules of immunodeficient mice for at least 17 weeks, and indicate that xenograft models are potentially useful for studying human follicle development. Using this physiological model, we showed that FSH is required for follicle growth beyond the two-layer stage, although growth initiation is independent of gonadotrophin stimulation.     

Improved oocyte quality is obtained with follicle stimulating hormone alone than with follicle stimulating hormone/human menopausal gonadotrophin combination

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH-stimulated patients.     

Ovarian hyperstimulation following the sole administration of agonistic analogues of gonadotrophin releasing hormone

Ovarian hyperstimulation following the sole administration of gonadotrophin-releasing hormone agonists (GnRHa) is exceedingly rare. We hereby report on two infertile patients undergoing in-vitro fertilization-embryo transfer who developed ovarian hyperstimulation under such circumstances. In both patients, GnRHa were administered using the 'long protocol' regimen. The first patient developed ovarian hyperstimulation on two occasions, with mid-luteal depot administration of triptorelin and with early follicular triptorelin, administered as daily subcutaneous injections. In both cycles, within 2 weeks of triptorelin therapy, massive ovarian multifollicular enlargement occurred, concomitant with high serum oestradiol concentrations, which resolved spontaneously following expectant management. The second patient developed ovarian hyperstimulation following daily injections of leuprolide acetate starting at the mid-luteal phase. The final stage of ovulation was triggered by human chorionic gonadotrophin (HCG) and 11 oocytes were retrieved. In-vitro fertilization resulted in embryo formation, but failed to result in pregnancy. The same phenomenon recurred in a subsequent cycle despite preventive pretreatment with an oral contraceptive. A negative GnRH test, performed just before HCG administration, suggested than an ongoing 'flare-up effect' was unlikely to cause ovarian stimulation. Ovarian hyperstimulation can occur following the sole administration of GnRHa irrespective of the preparation used and the administration protocol. Although spontaneous resolution is the rule, once this condition has developed, HCG administration and oocyte retrieval are feasible. This rare entity probably represents an exaggerated form of ovarian cyst formation following GnRHa administration, the underlying pathophysiology of which remains unresolved.     

Quick-FISH: a rapid fluorescence in situ hybridization technique for molecular cytogenetic analysis

OBJECTIVE: To evaluate the pregnancy results of an ovarian hyperstimulation protocol for IVF-ET that combines GnRH agonist down-regulation, cessation of GnRH agonist therapy with the onset of menstruation, and high-dose gonadotropin administration in low responders. DESIGN: Prospective analysis. SETTING: Academic IVF program. PATIENT(S): One hundred eighty-two low responders undergoing 224 IVF-ET cycles. INTERVENTION(S): Down-regulation was obtained with the administration of leuprolide acetate beginning in the midluteal phase and ending with the onset of menses. Daily administration of 6 ampules of FSH alone or in combination with hMG was initiated on cycle day 3. MAIN OUTCOME MEASURE(S): Stimulation characteristics and pregnancy rates (PRs) were compared between fresh cycles in which pure FSH alone was used and 35 cycles in which a combination of FSH and hMG was administered. RESULT(S): The clinical PR per transfer, the ongoing PR per transfer, and the implantation rate were 32%, 24%, and 9%, respectively. No differences were noted between cycles in which pure FSH alone was used in comparison with cycles in which a combination of FSH and hMG was administered. CONCLUSION(S): Short-term ovarian suppression begun in the luteal phase and discontinued with the onset of menses followed by high-dose stimulation with gonadotropins yields favorable pregnancy results in low responders.     

Endometrial and placental protein markers and ovarian steroids in serum during in-vitro fertilization cycles

The objective of this study was to find the earliest time at which it was possible to detect clinical pregnancy in an in-vitro fertilization (IVF) treatment cycle supported with human chorionic gonadotrophin (HCG), and also retrospectively to diagnose abnormal ovarian- or endometrium-related situations in failure cycles. Serum samples were taken in 41 IVF cycles at frequent intervals from the beginning of ovarian stimulation until menstrual bleeding occurred or a pregnancy was established. Concentrations of oestradiol, progesterone, placental protein 14 (PP14), pregnancy-specific beta 1-glycoprotein (SP1), and pregnancy-associated plasma protein A (PAPP-A) were determined in the serum samples using commercially available (steroid) or purpose-developed (protein) immunoassays. The cycles were retrospectively distributed into four outcome groups: (i) fertilization failure (FF, n = 8); (ii) implantation failure (IF, n = 10); (iii) 'interaction' (embryo-endometrium) cycle (IC, n = 14), and (iv) clinical pregnancy (CP, n = 9). The embryo-endometrium interaction was detected by a rise in SP1 in 23 cycles (70% of embryo transfers) at a time when endogenous HCG was still masked by external support. Early ('false') positive SP1 concentrations were observed in two out of eight and five out of 14 cases in groups FF and IC respectively, but never amongst the ongoing pregnancies (CP). PAPP-A did not distinguish pregnancy from the other outcomes. The PP14/progesterone ratio was lower, later in the cycle, in CP than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is luteal function maintained by factors other than chorionic gonadotrophin in early pregnancy?

Women with ectopic pregnancy (n = 14) and early embryonic arrest ('blighted ovum') (n = 9) were studied 16 days after conception, at a time when they were asymptomatic and serum concentrations of beta-human chorionic gonadotrophin (HCG) were in the normal range and increasing at an apparently normal rate. Serum progesterone and oestradiol concentrations were compared with those from normal women matched for gestational age and serum beta-HCG concentration whose singleton intra-uterine pregnancies proceeded normally beyond 20 weeks. Mean serum progesterone concentrations were significantly lower in the women with ectopic pregnancies than in matched controls (P < 0.002); however, there was no difference in the serum progesterone concentrations between women with blighted ova and matched controls. Statistically significant differences were not seen in serum oestradiol concentrations between either group and matched controls. Similarly there was no difference in serum progesterone or oestradiol concentrations in 20 women who conceived ectopic pregnancies and 20 women conceiving blighted ovum pregnancies and their matched intra-uterine controls when conception followed ovarian stimulation. The low serum progesterone concentrations seen in ectopic pregnancy suggest that there is a specific and selective deficiency in progesterone synthesis, which implies that factors other than HCG may influence luteal function.