Correlation of follicular diameter with oocyte recovery and maturity at the time of transvaginal follicular aspiration

Forty-four consecutive patients undergoing transvaginal follicular aspiration for in vitro fertilization underwent ultrasonic measurement of follicular diameter at the time of oocyte retrieval to determine the correlation of follicular size with recovery rates and oocyte maturity. Based on the results of 412 follicles aspirated, the data were grouped by size (11, 12–14, 15–17, 18–20, and 21 mm) and oocyte maturity. Recovery rates were significantly higher in 18- to 20-mm follicles (P<0.01) and lower in those 11 mm (P<0.001). The probability of retrieving a metaphase I or II oocyte was significantly lower in follicles 11 mm (P<0.001), somewhat higher in 12- to 14-mm follicles (P<0.01), and equally high among the other groups. There were no differences in the incidence of fractured zonas. We conclude that follicles 15 mm provide the highest probability of retrieving mature oocytes and the low recovery rates of mature oocytes from follicles 11 mm suggest that, in selected circumstances, the operating surgeon may choose not to aspirate them.     

Oocyte maturation inhibitor activity in human follicular fluid: Quantitative determination in unstimulated and clomiphene citrate- and human menopausal gonadotropin-stimulated ovarian cycles

Since removal of the oocyte from the intrafollicular milieu allows meiotic resumption and germinal vesical breakdown to proceed, the concept of an intrafollicular oocyte maturation inhibitor (OMI) has evolved. Accordingly, we asked the following questions: Is there OMI activity in human follicular fluid? Does OMI activity change with ovarian hyperstimulation? and Does OMI activity correlate with oocyte fertilization or the concentration of steroids in the corresponding follicular fluid? Fresh cumulus enclosed porcine oocytes from small follicles were incubated with human follicular fluid aspirates from normally menstruating patients with or without treatment: unstimulated follicles (N=10), clomiphene citrate (150 mg/day) (N=10)-treated cycles, and human menopausal gonadotropin (hMG) (N=12)-treated cycles. A lyophylized porcine follicular fluid standard and serum-free culture media were used as positive and negative controls, respectively. After a 40-hr incubation with test materials, the oocytes were fixed, stained, and evaluated for oocyte maturation as determined by germinal vesical breakdown. Human follicular fluid, estradiol, progesterone, androstenedione, and testosterone levels were determined by radioimmunoassay. The 50% inhibitory dose (ID₅₀) for OMI activity in follicular fluid from untreated, spontaneously menstruating women was less than that for follicular fluid from clomiphene-stimulated patients, which was less than that for follicular fluid from hMG-stimulated patients. The difference between OMI values from untreated and hMG-stimulated follicular fluids was statistically significant. Human oocytes removed from follicular fluid with higher OMI activity tended not to fertilize in vitro compared to the relatively lower OMI activity present in follicular fluid yielding oocytes which did fertilize. However, these differences were not significant. Although there were no significant correlations between any of the follicular fluid concentrations of sex steroids and OMI activity, there was a trend toward higher androgen levels in follicular fluid with higher OMI activity. These findings lend support to the hypothesis that immature, nonfertilizable follicles obtained from spontaneously cycling women with or without exogenous gonadotropin treatment contain higher OMI activity levels than mature, fertilizable follicles.     

Correlation between follicular diameters and flushing versus no flushing on oocyte maturity,fertilization rate and embryo quality

Objective

To determine (a) the correlation between follicular sizes, oocyte maturity, normal fertilization rate, cleavage and embryo quality; and (b) to establish whether oocytes recovered with or without follicular flushing have different developmental competence.

Design

Prospective observational study.

Setting

Academic medical center.

Patients

Forty nine cycles (37 ICSI and 12 IVF).

Interventions

Measurement of 360 follicular diameters on the day of egg retrieval and classification into three groups Group A (mean diameter 12–14.5 mm.), group B (mean diameter 15–18 mm.) and group C (diameter >18.5 mm.).

Main outcome measure

Correlation between follicular size at the time of retrieval and oocyte maturity, fertilization and cleavage rate in 226 oocytes (163 ICSI and 63 IVF). Developmental competence of oocytes retrieved with flushing versus non flushing.

Results

Almost all (99 %) of the oocytes recovered from follicles of group C were in metaphase II as opposed to 80 % in group A and 81 % in group B (p < 0.01). Overall there was a progressive and significant increase in fertilization rates from group A follicles to group C (47 % vs. 67 %, p 0.05). Overall 53 % of oocytes retrieved from group A follicles showed either no fertilization or abnormal fertilization versus 27 % in group C (p 0.05). The oocyte recovery rate with follicular flushing improved from group A to group B and to group C follicles (65 % vs. 49 % vs.37 % respectively p < 0.01). There were no differences in rates of immature oocyte, fertilization, abnormal or not fertilization and cleavage.

Conclusions

The results of this study shows that: a) Follicles larger than 18 mm at retrieval have consistently mature oocytes with a higher rate of fertilization; b) Small size follicles are still capable of containing mature oocytes, but their rate of abnormal or no fertilization is high; c) Oocytes recovered with flushing are still able to produce embryos with full developmental competence.     

Follicular fluid transferrin levels in preovulatory human follicles

There is transferrin-like protein present in the follicular fluid of stimulated ovarian cycles. The transferrin concentration correlates with the follicular morphologic maturity and steroidogenesis, varies among follicles, and often exceeds serum concentrations. An intermediate range of transferrin concentration is associated with the highest likelihood of oocyte fertilization in vitro. The biological significance of these observations may relate to an optimum degree of follicle maturation.     

Follicular fluid nitric oxide (NO) concentrations in stimulated cycles: the relationship to embryo grading

Objective The microenvironment of the ovarian follicle is vital for normal oocyte development, folliculogenesis, and timely ovulation. We investigated the concentration of nitric oxide (NO) in follicular fluid, collected during oocyte retrieval after in-vitro fertilization and embryo transfer (IVF-ET) and its relationship to oocyte and embryo grading. Methods A total of 53 follicular fluid samples were obtained from 15 patients undergoing IVF-ET program, oocyte retrieval by transvaginal guidance was per formed approximately 34–35 h after the hCG administration in stimulated cycles. Using a modified grading system the samples were divided in Group 1 with very few fragments in the cytoplasm with equal size blastomeres (best embryos) and Group 2 with significant or severe fragmentation or blastomeres of distinctively unequal size. Follicular NO was measured as nitrite/nitrate. Results The mean concentration of NO follicular fluid is significantly higher in Group 2 than in Group 1 (57.54 ± 12.67 nmol/mg vs. 42.43 ± 16.32 nmol/mg). Using the correlation analysis, we observed a direct correlation between follicular NO and embryo grading (r = 0.61; P < 0.001) and an inverse correlation between follicular NO and serum 17beta-estradiol (r = −0.28; P < 0.05). Conclusions High levels of NO in human follicles may be detrimental. The inverse correlation found between NO and serum concentrations of 17beta-estradiol may be explained as a regulation of estradiol on maturation process of the oocytes and embryos in stimulated cycles through NO mediation.     

Serum steroids concentration might be used for monitoring the growth of follicles in friendly in vitro fertilization

Background:  Steroid levels have been used as the predictive parameters for oocyte maturation and embryo development. In the present study, estradiol and progesterone concentrations in the follicular fluid and serum were evaluated in conventional in vitro fertilization (IVF; follicle stimulating hormone [FSH] and/or human menopausal gonadotropin [hMG] after pituitary desensitization) and friendly IVF (no stimulation, clomiphene citrate, small dose of FSH or hMG without pituitary desensitization). The purpose of the present study was to evaluate the differences in steroid distribution between conventional and friendly IVF.
Methods:  Concentrations of estradiol, progesterone, FSH, and luteinizing hormone (LH) in serum and follicular fluid were determined in conventional and friendly IVF protocols by an enzyme-linked immunosorbent assay kit. Correlations between follicular fluid and serum steroid concentrations in these different protocols, and between pregnant cycles and steroid concentrations were evaluated.
Results:  Two hundred and thirty-four samples of follicular fluid from 74 IVF patients were analyzed. In conventional IVF, there was no relationship in steroid levels in between follicular fluid and serum steroids, whereas serum steroid concentrations correlated with the number of developing follicles. There was a relationship between the serum and follicular fluid estradiol levels ( r  = 0.467, P  < 0.0001) as well as progesterone levels ( r  = 0.227, P  = 0.0488) from friendly IVF patients.
Conclusions:  Serum steroid concentrations were mainly associated with the number of developing follicles. In the cases of friendly IVF, which had a small number of developing follicles, serum steroids might be used to monitor follicular fluid steroid concentrations. (Reprod Med Biol 2006; 5 : 277–282)     

Premature LH and progesterone rise in intrauterine insemination cycles: analysis of related factors

Premature LH and progesterone surges are associated with different factors and hormonal modulators. The aim of the present study was (i) to investigate the clinical and laboratory factors and (ii) to highlight the importance of different stimulation protocols in associated premature LH and progesterone surges in intrauterine insemination (IUI) cycles. The study involved a retrospective investigation of 75 patients undergoing IUI for infertility treatment (135 IUI cycles) between 1996 and 2000, with initial serum LH concentrations >10 mIU/ml during ovarian stimulation. Ultrasound characteristics, follicular sizes, serum oestradiol, progesterone and LH concentrations and ovarian stimulation protocols were measured. There was a wide range of oestradiol serum concentrations (93-2245 pg/ml) and follicular size (12-25 mm). In 49.6% of cycles, the dominant follicle was <16.5 mm. Patients with >2 follicles measuring <15 mm had higher oestradiol serum concentrations (P = 0.008). Multiple regression analyses revealed no association between these variables and premature LH/progesterone surge. In conclusion, LH/progesterone surges cannot be predicted utilizing clinical parameters normally employed, e.g. ultrasound serum oestradiol assay or ovarian stimulation protocol. Patients with follicles >14 mm or more and with high numbers of small follicles and high oestradiol are at risk of a spontaneous LH surge. These variables can be used to time the administration of GnRH antagonist administration until better predictive factors are demonstrated.     

The effect of a prolonged artificial follicular phase on endometrial development in an oocyte donation program

Stretching the duration of an artificial follicular phase in an oocyte donation program facilitates greatly the synchronization between the donor and the recipient. In order to investigate the limits of such a prolonged endopetrial preparation, 18 patients with ovarian failure were studied during 20 treatment cycles. These patients were prospectively and randomly divided into three groups (A, B, and C in eight, six, and six cycles respectively). All groups were treated with oral estradiol and estriol (at a 21 ratio_, 4 mg/day for 21, 28, and 35 days, respectively. At this stage 50 mg/day of intramuscular progesterone was added for additional 7 days. Endometrial adequacy was evaluated by late follicular and midluteal endometrial biopsies. During treatment no patient suffered from breakthrough bleeding. The mean estradiol and progesterone levels during the follicular and luteal phases did not differ significantly between groups. All late follicular biopsies showed a normal proliferative endometrium with no signs of glandular cystic hyperplasia. The midluteal biopsy showed a secretory endometrium adequate for 18.6±1.8, 21.8±1.8, and 18.6±1.5 days in groups A, B, and C, respectively, with no significant glandularstromal disparity. We conclude that an artificial prolonged follicular phase does not seem to affect adversely the endometrilar preparation in an oocyte donation program.     

Human follicular fluid proteoglycans in relation to in vitro fertilization

Objective: To determine whether the concentrations of proteoglycans and hyaluronan in human follicular fluid (FF) are associated with follicular volume, oocyte fertilization, and ET during IVF.Design: The FF from individual follicles were collected. Enzyme-linked immunosorbent assay methods for quantification of a larger chondroitin sulfate proteoglycan and a smaller composite heparan-chondroitin sulfate proteoglycan were established. Hyaluronan and E₂ were measured by RIA techniques.Patient(s): Sixteen infertile women participating in the IVF program.Main Outcome Measure(s): Concentrations of the proteoglycans, follicular volume, fertilization, and ET rates.Result(s): The follicles contained high concentrations of proteoglycans with an average of 0.8 mg/mL of FF, and approximately 70% consisted of the larger chondroitin sulfate proteoglycan, and 30% of the heparan-chondroitin sulfate proteoglycan. A negative correlation was found between the follicular volume, the chondroitin sulfate proteoglycan (r = −0.43), and hyaluronan (r = −0.56). The percentage of embryos developed in culture was significantly higher in follicles larger than 2 mL. A significant and 35% lower concentration of the chondroitin sulfate proteoglycan was found in larger follicles from which subsequent ET was observed. The heparan-chondroitin sulfate proteoglycan and hyaluronan were both unrelated to fertilization and ET in vitro.Conclusion(s): Lower concentrations of chondroitin sulfate proteoglycan were associated with higher follicular volumes and greater fertilization and ET rates. These associations could merely reflect the maturation of the follicle or a role of the chondroitin sulfate proteoglycan in the fertilization process.     

Inhibin B predicts oocyte number and the ratio IGF-I/IGFBP-1 may indicate oocyte quality during ovarian hyperstimulation for in vitro fertilization

Purpose: To perform a retrospective analysis of 62 age-matched IVF-treated women in order to investigate whether levels of inhibin B, IGF-I, and IGFBP-1 in serum 2 days before oocyte retrieval and in follicular fluid at the day of oocyte retrieval might be useful as indicators of the ovarian ability to produce oocytes (ovarian reserve). Methods: Patients were allocated into three groups on the basis of the number of oocytes retrieved. Group 1 (low responders) had 0–3 oocytes, group 2 (normal responders) had 6–11 oocytes, and group 3 (high responders) had 12 oocytes or more. Levels of inhibin B, IGF-I, and IGFBP-1 in follicular fluid and in serum obtained 2 days before oocyte retrieval were analyzed and correlated to clinical parameters including estradiol levels, progesterone levels, follicle size, follicle number, and oocyte number. Results: We found significant differences in inhibin B levels in the three groups. Inhibin B levels in follicular fluid and serum was strongly correlated to the number of oocytes retrieved (p < 0.01). The number of oocytes retrieved were also correlated to total FSH dose (p < 0.05), to estradiol 2 days before and at ovum pick-up (p < 0.05), to progesterone at ovum pick-up (p < 0.0001), to progesterone at embryo transfer (p < 0.05), and to the number of follicles (size 12–15 mm, p < 0.001, size>15 mm, p < 0.01). Serum inhibin B also correlated to follicular fluid inhibin B (p < 0.01). Inhibin B was not correlated to pregnancy. In contrast, the ratio IGF-I/IGFBP-1 in serum as well as in follicular fluid was significantly higher in women who became pregnant (p < 0.05). Conclusions: The results show that inhibin B in serum 2 days before oocyte retrieval predicts number of oocytes retrieved. Since inhibin B in serum before oocyte retrieval in ovarian hyperstimulation was strongly predictive of the number of oocytes retrieved, it appears useful as a marker for ovarian response. Inhibin B did not predict treatment outcome, whereas the ratio IGF-I/IGFBP-1 in serum and follicular fluid was significantly higher in women who became pregnant. The ratio IGF-I/IGFBP-1 may thus reflect oocyte quality.     

A proteomic analysis of human follicular fluid: comparison between fertilized oocytes and non-fertilized oocytes in the same patient

Purpose

Human follicular fluid constitutes the microenvironment of follicles and includes various biological active proteins that can affect follicle growth and oocyte fertilization. Conducting proteomic evaluations of human follicular fluid may be helpful for identifying potential biomarkers possibly possessing a predictive value for oocyte quality and the success of in vitro fertilization.

Method

We performed proteomic profiling of human follicular fluids containing oocytes that were fertilized and resulted in pregnancy and follicular fluids containing oocytes that were not fertilized in the same patients undergoing intracytoplasmic sperm injection using the LTQ Orbitrap coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS) analyses.

Results

We identified a total of 503 proteins in human follicular fluids containing fertilized and non-fertilized oocytes obtained from 12 patients. We also found that 53 proteins exhibited significantly different spectral counts between the two groups, including heparan sulfate proteoglycan perlecan, which showed significant upregulation in the follicular fluids containing fertilized oocytes in comparison with that observed in the follicular fluids containing non-fertilized oocytes.

Conclusion

Our results suggest a possibility that proteins identified by LC/MS/MS in follicular fluid might not only be involved in folliculogenesis, but also function as biomarkers possessing predictive potential for oocyte maturation and the success of IVF when their expression levels are significantly different between fertilized and non-fertilized oocytes, although no distinctive biomarkers were identified in the current study.     

Serum progesterone concentrations on the day after human chorionic gonadotropin administration and progesterone/oocyte ratios predict in vitro fertilization/embryo transfer outcome

Purpose In gonadotropin-releasing hormone analogue-pretreated in vitro fertilization-embryo transfer cycles, pregnancy rates are inversely related to serum progesterone levels on the day of administration of human chorionic gonadotropin. The relationship of the progesterone concentration on other days in the periovulatory period to pregnancy rates in such cycles is little studied. We therefore retrospectively analyzed the relationship between progesterone concentrations on the day after human chorionic gonadotropin and pregnancy in 114 cycles, 28 and 23 of which produced clinical and ongoing/delivered pregnancies, respectively. To assess the effect of the extent of follicular luteinization on success, we also studied the relationship between the progesterone concentration per oocyte retrieved and pregnancy for the day of and day after human chorionic gonadotropin.Results Progesterone concentrations on the day after human chorionic gonadotropin were inversely associated with clinical pregnancy by multiple logistic regression analysis (P<0.05). Progesterone/oocyte ratios were inversely associated with clinical pregnancy (P<0.05) and ongoing/delivered pregnancy (P<0.02) for both the day of and the day after human chorionic gonadotropin.Conclusion The study results extend the window of time during which elevated progesterone concentration is associated with poor outcome to at least 2 days. This finding is consistent with hypothetical mechanisms attributing the link between progesterone concentration and outcome to either endometrial or follicle/oocyte events. The association of lack of follicular luteinization (low progesterone per oocyte ratios) and favorable outcome suggests a predominant effect of progesterone on follicle/oocyte quality. Further studies are needed to clarify the mechanisms underlying the association between progesterone and in vitro fertilization-embryo transfer outcome.     

Immunoreactive epidermal growth factor concentrations in follicular fluid obtained from in vitro fertilization

Immunoreactive epidermal growth factor (EGF) was measured in follicular fluid (FF) obtained at the time of oocyte retrieval for in vitro fertilization from cycles with (91 follicles) and without (128 follicles) the gonadotropin-releasing hormone agonist leuprolide acetate (LA). Follicular fluid immunoreactive EGF levels in the non-LA cycles correlated with androstenedione but not estradiol or progesterone levels from follicles with prophase I oocytes or from all follicles taken together, but not from metaphase I or metaphase II oocyte containing follicles alone. In non-LA cycles, FF immunoreactive EGF levels were lower in follicles that contained metaphase I or II oocytes than prophase I oocytes. Additionally, FF immunoreactive EGF levels were lower in follicles containing metaphase I or II oocytes from non-LA than LA cycles. We conclude that immunoreactive EGF is present in FF. Leuprolide acetate may affect FF immunoreactive EGF levels.     

Relationship between the steroid and prolactin concentration in follicular fluid and the maturation and fertilizaton of human oocytes

Seventyeight follicles and their follicular fluid were aspirated from 46 women undergoing in vitro fertilization (IVF) procedures after stimulation of the ovaries with a low-dose human menopausal gonadotropin/human chorionic gonadotropin stimulation regimen. The concentrations of estradiol (E₂), progesterone (P), testosterone (T), and prolactin (PRL) were measured in follicular fluid and related to the maturation of the oocyte-corona-cumulus complex (OCCC) and the fertilization of oocytes. Follicles containing mature oocytes had significantly higher follicular fluid E₂ and P levels than follicles with intermediate and immature oocytes. A constant decrease in PRL and T values with advancing follicular maturation was observed. Similar results were obtained when the fertilizing ability of the oocytes was examined. The gradual decline in follicular fluid PRL and T levels during follicular development was connected with increasing E₂ and P biosynthesis and therefore seems to be an important precondition for normal follicular and oocyte maturation.     

Correlation between human follicular diameter and oocyte outcomes in an ICSI program

Purpose: To determine the correlation between the follicular sizes and oocyte recovery, metaphase II oocyte recovery, fertilization rate and good embryo quality from mature and immature oocytes in an intracytoplasmic sperm injection (ICSI) program. Methods: 991 follicles obtained from 72 ICSI cycles were classified into three groups according to their diameters as measured by transvaginal ultrasound including group A (<10 mm), group B (10–14 mm), and group C (>14 mm). All obtained oocytes were classified according to their nuclear maturation: germinal vesicle (GV), metaphase I (MI) and metaphase II (MII). Mature oocytes underwent ICSI while immature oocytes were further cultured until maturity before ICSI was performed. The rates of fertilization and good quality embryos at day 3 were evaluated. Results: A progressive and significant increase in the rates of oocyte recovery and MII oocyte recovery were observed from group A follicles compared to the other groups (p < 0.001). The fertilization rate of mature and in vitro matured oocytes, as well as the rate of good quality embryos showed a tendency to increase from group A to group C follicles, but not significantly. The corresponding fertilization rates were 78 and 55.3% (p < 0.001) for mature and in vitro matured oocytes, respectively. Conclusion: Collection of oocytes from small follicles, especially with a mean diameter less than 10 mm, and in vitro maturation of immature oocytes before fertilization may allow the total number of good quality and transferable embryos to be increased.     

Intraovarian markers of follicular and oocyte maturation

The use of ovulation induction for multiple follicular growth in in vitro fertilization (IVF) has introduced the problem of follicular asynchrony. As a consequence of the asynchrony, the parameters most commonly used by IVF groups to assess follicular and oocyte quality within those follicles are not sufficiently sensitive or specific. Thus, each follicle must be considered separately, and specific markers of follicular and/or oocyte maturation must be sought from within the follicle. In this review we analyze previous reports of potential markers of follicular and oocyte maturation. In regards to the follicular fluid constituents, the level of estradiol in follicular fluid correlates with fertilization and pregnancy in stimulated cycles. Other steroids are only helpful when specific stimulation protocols are used. The level of some follicular proteins such as alpha-1-antitrypsin and fibrinogen also correlates with fertilization and pregnancy outcome. Cyclic AMP levels in follicular fluid are significantly reduced in follicles leading to conception. Regulators of oocyte maturation, such as the Oocyte Maturation Inhibitor (OMI) or the Meiosis Inducing Substance (MIS) have also been correlated with IVF outcome, but their exact structure remains still unknown. In addition, other sophisticated parameters, such as chemotactic activity of human leukocytes, or simple methods, such as the presence of intrafollicular echoes, have also been used as successful markers in predicting IVF outcome.     

Interleukin 15 concentrations in follicular fluid and their effect on oocyte maturation in subfertile women undergoing intracytoplasmic sperm injection

Purpose

To calculate the concentrations of interleukin 15 (IL-15) in follicular fluid (FF) and evaluate their relation with oocyte maturation, follicle size, and patients’ body mass index (BMI) and age.

Methods

Follicular fluid specimens were obtained from 56 subfertile women undergoing intracytoplasmic sperm injection (ICSI) during oocyte retrieval for measurement of IL-15 concentrations with ELISA. Wilcoxon’s test and Pearson’s correlation coefficient were used to correlate FF concentrations of IL-15 with follicular size and stage of oocyte maturation, along with patients’ BMI and age.

Results

IL-15 concentrations in FF of follicles with immature oocytes were significantly greater than those from follicles with mature ones (median 5.333 vs. 3.250 pg/ml, respectively, p?<?0.001). There was a significant negative correlation between IL-15 concentrations and follicle size (r?=???0.333, p?=?0.003). No significant correlation was observed between IL-15 concentrations and patients’ BMI and age (p?>?0.05).

Conclusions

IL-15 concentrations in FF are adversely related with the size of the follicles and the maturity of the corresponding retrieved oocytes in a cohort of expected normal responders undergoing intracytoplasmic sperm injection (ICSI). Follicular fluid concentrations of IL-15 should be investigated as a possible predictive factor for oocyte maturity.

     

Protein composition of follicular fluid and oocyte cleavage occurrence in in vitro fertilization (IVF)

The present study was carried out from in vitro fertilization (IVF) attempts to analyze further the total and specific protein contents of 47 follicular fluids yielding one oocyte. The aim was to find correlations between the follicular concentrations of such proteins and the occurrence of coupled oocyte cleavage. These findings would be used as markers of IVF outcome. Two groups of follicular samples were distinguished: one group with cleavage occurrence (25 cases) and another group without cleavage or even fertilization (22 cases). In the group with cleavage a significantly higher level was observed for six proteins: C3 complement fraction and ceruleoplasmin (P <0.02), -antitrypsin and transferrin (P <0.01), and 2-macroglobulin and 2-microglobulin (P <0.001). The data are discussed with respect to changes in follicle permeability with advancing maturity.     

Uterine arterial blood flow and the substances of ovarian renin-angiotensin system in women with polycystic ovaries undergoing in vitro fertilization

OBJECTIVE: To find whether plasma and follicular prorenin concentrations have any effect on the uterine arterial blood flow in women with polycystic ovarian syndrome (PCOS) compared to those with normal menstrual cycles (NMC). STUDY DESIGN: Controlled prospective clinical study involved 55 women undergoing in vitro fertilization: 24 with PCOS and 31 with NMC. In both groups transvaginal colour Doppler assessment of uterine arterial blood flow was analysed on day 22 of the cycle, on the day of human chorionic gonadotrophin (HCG) administration and 36 h after HCG. Plasma and follicular (in the dominant follicle containing mature oocyte, and in the pooled follicles) prorenin and active renin, and serum estradiol and androstenedione concentrations were measured at these time-points. The Student's t-test and Pearson correlation were used for the statistical analysis. RESULTS: The resistance index (RI) in the NMC group decreased from 0.84+/-0.05 on the day of HCG to 0.78+/-0.08 36 h after HCG (P < 0.05); in the PCOS group the RI did not decrease. Follicular prorenin concentrations in the dominant follicle and in the pooled follicles were lower in the PCOS than in the NMC group (20,210+/-10,831 microU/l, 16,753+/-8634 microU/l versus 42,637+/-35,400 microU/l, 33,067+/-26,200 microU/l; P < 0.05). CONCLUSIONS: Plasma prorenin concentrations do not affect vascular impedance to the uterine artery, but follicular prorenin do by newly formed low resistant vessels in the follicles.     

The day of initiation of human menopausal gonadotropin stimulation affects follicular growth in in vitro fertilization cycles

The attainment of synchronous follicular development in human menopausal gonadotropin/human chorionic gonadotropin-stimulated cycles for in vitro fertilization (IVF) continues to be a perplexing problem. Two regimens of follicle stimulation for IVF cycles were, therefore, compared. Twenty-nine patients commenced human menopausal gonadotropin (hMG) therapy on day I of the menstrual cycle (Group I), while 30 women received hMG from the third day of the cycle (Group II). The hMG therapy was tailored to the individual patients's response, based on ultrasonographic measurements of follicular size and serum estradiol (E₂) levels. Both groups of patients received a mean of 19.6±1.4 ampules of hMG over a mean of 6.1±0.2 days. The pattern of serum E₂ and progesterone levels in the periovulatory and luteal phase was not affected by the day of initiation of hMG therapy, although Group I patients demonstrated lower (P<0.05) E₂ levels on the 2 days prior to human chorionic gonadotropin (hCG) administration. In terms of follicle growth, Group II follicles consistently demonstrated a significantly (P<0.01,x ² test) larger proportion of medium- and large-sized follicles compared to Group I follicles on almost all of the days when ultrasonographic measurements were taken. In addition. Group II follicles demonstrated an earlier shift (day—1) to the larger follicles than Group I follicles (day 0). Significantly (P<0.001) more oocytes were recovered per uspirated follicle in Group II patients, but the fertilization rate per oocyte was greater (P<0.003) for Group I oocytes. Nevertheless, pregnancy rates did not differ between the two groups. It is suggested that a difference between the two groups of patients in the quantity or quality of gonadotropin receptor sites in the early part of the follicular phase may account for both the diminished E₂ production in the follicular phase and the persistent depressed follicular growth in Group I patients.