Preferential transfer of endogenous ovarian steroid hormones to the uterus during both the follicular and luteal phases

BACKGROUND: Ovarian steroids are thought to be released into the systemic circulation and reach the uterus via the uterine arteries. However, results of experimental and clinical studies suggest the existence of local transfer of steroids from the ovary to the uterus. This study aimed to verify the existence of preferential distribution of ovarian steroids to the uterus in the two phases of the menstrual cycle. METHODS: We performed parallel measurements of serum levels of estradiol and progesterone in the systemic circulation (arterial and venous) and in the uterine vessels in two groups of cycling women; one group were in the follicular phase (six women) and the other group were in the luteal phase (10 women) of the menstrual cycle. RESULTS: Both in the follicular phase and in the luteal phase groups, mean estradiol levels in the uterine blood were significantly higher than in both sides of the systemic circulation (F = 7.30, df = 15, P < 0.006; and F = 4.70, df = 27, P < 0.02). Similar results were obtained in the luteal phase group for progesterone (F = 9.38, df = 27, P < 0.0001). Both estradiol and progesterone levels in arterial and venous systemic blood were similar. CONCLUSIONS: The results of this study demonstrate that ovarian steroid levels are significantly higher in the uterine vessels than in both sides of the systemic blood circulation, and strongly suggest the existence in the female pelvis of mechanisms of local distribution of ovarian hormones.     

Uterine first pass effect in postmenopausal women

BACKGROUND: Vaginally administered drugs distribute preferentially to the uterus; counter-current transfer from the vaginal veins to the uterine artery probably plays a pivotal role. In each side, the ovarian and uterine arteries form arterial anastomoses and controversy exists regarding the origin of the arterial supply to the Fallopian tube and tubal part of the uterus, and consequently whether these tissues can be reached through vaginal administration. METHODS: A thermocatheter with four measurement points, each separated by 5 mm, was inserted under endoscopic control into the tubal corner of uterus in 10 conscious, menopausal women and the temperatures registered every 2 s. The vagina was then flushed for 15 min with 1.5 l of saline at room temperature, after which the probe position was re-assessed by the endoscope. RESULTS: The lowest measurement point (15 mm from the tip) cooled significantly more than the other points (P < 0.0001). At 15 min, mean temperature reduction at point 4 was significantly greater than at all other measurement points (P < 0.05) due to local transfer of cold from vaginal vein blood to the uterine arterial blood (but not the ovarian artery). CONCLUSIONS: The results support the theory that, at least in postmenopausal women, the uterine artery supplies most of the uterus while the corneal part of cavity (up to 5-10 mm from the ostium) receives the blood supply from the ovarian artery. This finding represents a rationale for vaginal administration of drugs when a local effect on the uterus (e.g. progestational or relaxation) in postmenopausal women is requested.     

A dominant ovarian follicle induces unilateral changes in the origin of the blood supply to the tubal corner of the uterus

BACKGROUND: The blood supply to the tubal corner of the uterus may originate from the uterine and ovarian arteries. The border of supply from the arteries has been found to move in young women; the change seemed dependent on ovarian steroid production. The present work investigated whether the border of supply could differ between the two sides of the uterus in the same woman having one dominant follicle (>10 mm). METHODS: Vagina was flushed with saline of room temperature in 15 women with a dominant follicle >10 mm. The temperature was measured in the mid-uterine lumen and in the tubal corner of the uterus at 2, 5 and 7 min after starting cooling. The investigation was repeated 30 min later measuring the temperature in the other tubal corner. RESULTS: The temperature decrease was, as found in previous investigations, more pronounced in the uterine cavity than in the tubal corners. However, a difference was found between the two tubal corners. At all measurement times the decrease was significantly smaller in the tubal corner corresponding to the dominant follicle than in the contralateral side. CONCLUSIONS: In our model, 'cold' is transferred from the vaginal venous blood to the uterine artery and the cooling defines the supply area of the uterine artery. Therefore, the results indicate that the area of supply from the ovarian artery in the tubal corner ipsilateral to the dominant follicle is greater than that in the contralateral side. It is possible to speculate that this difference is related to the hormonal production of the dominant follicle.     

Cytokine production by natural killer lymphocytes in follicular and luteal phase of the ovarian cycle in humans

PROBLEM: The aim of this study was to test the hypothesis that, during luteal phase of the ovarian cycle, as compared with follicular phase, the cytokine productive capacity of peripheral natural killer (NK)-lymphocytes in humans is shifted towards a "Th2-type"-like response. METHOD OF STUDY: Intracellular Th1 and Th2 cytokine production by in vitro activated peripheral NK-lymphocytes in a whole blood preparation of the follicular and the luteal phase of the ovarian cycle was measured by flow cytometry. RESULTS: There was no difference in interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 cytokine production in activated NK-lymphocytes when comparing luteal phase with follicular phase of the ovarian cycle. However, there was a significant increase in peripheral NK-lymphocyte number in luteal phase compared with follicular phase. CONCLUSION: The cytokine productive capacity of peripheral NK-lymphocytes is not shifted towards a "Th2-type"-like response in the luteal phase as compared with the follicular phase of the ovarian cycle in humans.     

Successful uterine transplantation in the mouse: pregnancy and post-natal development of offspring

BACKGROUND: Uterine transplantation could serve as a tool in studies of the physiology of implantation/pregnancy, and is also a possible future treatment for patients with absolute uterine infertility. Here, the first live-born offspring in any uterine transplantation model is reported. METHODS: A syngeneic mouse model with a uterus transplanted, by end-to-side aorta/vena cava vascular anastomoses, alongside the native uterus was used. The cervix was attached to a cutaneous stoma. Pregnancy rate and offspring (birth weight, growth and fertility) was evaluated after blastocyst transfer to the native and the grafted uterus of transplanted mice and to controls. RESULTS: Pregnancy rates were comparable in the grafted uterus (8/12 animals became pregnant) and the native uterus (9/12 pregnant) of transplanted animals and controls (8/13 pregnant). In a separate set of animals, the native uterus was removed at transplantation to exclude influences from the native uterus on the pregnancy potential of the graft; two of four animals became pregnant after blastocyst transfer. The weights/lengths of fetuses (gestational day 18) and gestational lengths were similar in all groups. Offspring were delivered and the growth trajectories (up to 8 weeks) of offspring delivered from grafted or native uteri of transplanted mice were similar as compared with controls, and all were fertile. The second-generation offspring from transplanted animals were all fertile with normal birth weights. CONCLUSIONS: These observations document the capacity of a transplanted uterus to harbour pregnancies to term, and reveal that offspring from a transplanted uterus develop to normal fertile adults.     

Highly efficient and minimally invasive in-vivo gene transfer to the mouse uterus using haemagglutinating virus of Japan (HVJ) envelope vector

The uterus is obviously critical in implantation, development of the fetus and parturition. Endometrial cancer derived from endometrial epithelium is one of the common malignancies in the female reproductive tract. In order to clarify the local mechanisms of reproductive physiology and establish a non-systemic therapeutic strategy for reproductive failure as well as for endometrial cancer, we applied haemagglutinating virus of Japan envelope (HVJ-E) vector to in-vivo gene transfer into the uterine cavity of IVCS mice. Injection of HVJ-E vector into mouse uterine cavity on day 1.5 post coitum (p.c.) introduced a reporter gene approximately 120-fold more efficiently than introduction using the cationic liposome method. The expression of the introduced gene continued for at least 3 days. The plasmid vector was localized in the endometrial epithelium, whereas oligo deoxynucleotides were distributed throughout the epithelium, stromal cells and myometrium. HVJ-E vector did not affect the pregnancy rate, course of pregnancy, litter size, fetal growth in utero or parturition, and did not transfect the exogenous gene to the fetus. These results indicate that gene transfer into the uterus using HVJ-E vector is highly efficient and safe during pregnancy, and results in a well controlled distribution of the exogenous DNA. We believe that this procedure should be widely applicable for investigations of reproductive physiology as well as for methods of local gene therapy in the uterus.     

Luteal phase ovarian oestrogen is not essential for implantation and maintenance of pregnancy from surrogate embryo transfer in the rhesus monkey

The aim of this study was to investigate whether luteal phaseovarian oestrogen is required for blastocyst implantation andpregnancy maintenance in the rhesus monkey. Preimplantationembryos were retrieved from naturally ovulated, mated embryodonor monkeys. In group I, developmentally normal, age- andstage-matched embryos were transferred to recipient monkeysshowing naturally synchronized ovulatory cycles. Immediatelyprior to embryo transfer, recipients were subjected to bilateralovariectomy, and following transfer they were treated with i.m.injections of either progesterone (group Ia, n= 4), or oestradiol+ progesterone (group Ib, n= 2). Recipient monkeys of groupIc (n= 4) were subjected to sham ovariectomy and vehicle injection.In group Ia, progesterone supplementation alone led to threepregnancies and live births. In group Ib, there was one livebirth. In the control group Ic, four transfers resulted in twolive births and one abortion on cycle day 58. Analysis of serumprogesterone and oestradiol profiles showed that oestradiolhad declined to undetectable levels within 3–5 days afterovariectomy in group Ia recipients, and the area under the curveof serum oestrogen concentrations during the peri-implantationperiod (days 10–20 after ovulation) were less (p< 0.001)in group Ia compared with group Ic. There were no changes inthe area under the curve among serum progesterone concentrationsin all the subgroups. In group II, long-term ovariectomizedembryo recipients (n= 4) were primed with oestradiol till cycleday 11 of simulated transfer cycle, and received progesteronetreatment from cycle day 10 till the end of the experiment.Of four transfers, live births were recorded in two cases, whilein one case abortion occurred on cycle day 66. Serum oestradiolconcentrations were undetectable during the presumptive peri-implantationperiod of pregnancy cycles in group II recipient monkeys. Noyes‘dating of endometrial samples collected from both groups ondays 5–7 after the oestrogen rise revealed that endometrialhistology synchronized well with those found during days 3–5after ovulation in normal menstrual cycle. We conclude thatluteal phase ovarian oestrogen is not essential for progesterone-dependentendometrial receptivity and response leading to implantationand pregnancy maintenance in the rhesus monkey.     

Evidence of differential control of FSH and LH responses to GnRH by ovarian steroids in the luteal phase of the cycle

BACKGROUND: It is known that during the follicular phase of the cycle, estradiol sensitizes the pituitary to GnRH. The aim of this study was to determine the role of ovarian steroids in the control of GnRH-induced gonadotrophin secretion in the luteal phase of the cycle. METHODS: Eighteen normally cycling women were studied during the week following bilateral ovariectomy plus hysterectomy performed in early to mid-luteal phase. Six of the women received no hormonal treatment post-operatively (group 1, control), six received estradiol through skin patches (group 2) and the remaining six received estradiol plus progesterone (group 3). In all women the response at 30 min of LH (deltadeltaLH) and FSH (deltadeltaFSH) to GnRH (10 microg i.v.) was investigated on a daily basis. RESULTS: In group 1, serum FSH, LH and deltadeltaFSH values increased progressively following ovariectomy, while in groups 2 and 3 this increase was postponed or abolished. In contrast to deltadeltaFSH, deltadeltaLH values showed the same pattern of changes in all three groups with a significant decline up to post-operative day 4 and a gradual increase thereafter. CONCLUSIONS: These results demonstrate, for the first time, that in the early to mid-luteal phase of the cycle, estradiol and progesterone participate in the control of GnRH-induced FSH, but not LH, secretion. It is possible that in the luteal phase, the response of LH to GnRH is partly regulated by gonadotrophin surge attenuating factor.     

Physiological and pharmacological aspects of local transfer of substances in the ovarian adnexa in women

An intimate arrangement between the utero-ovarian vein and the ovarian artery has been found in many species. The anatomical structure suggests the existence of a counter-current system of exchange, and many animal experiments point to a physiological importance of this transfer system. In man, the utero-ovarian vein forms a plexus around the ovarian artery. In-vitro experiments have demonstrated a local transfer of progesterone; in-vivo experiments have proved that krypton and progesterone can be transferred from the utero-ovarian vein to the ovarian artery. The physiological and pharmacological importance of the counter-current system is still under evaluation, and further investigations are needed. It has been suggested that counter-current transfer facilitates local communication between the ovary, Fallopian tube, and uterus. This may be important in a context of luteolysis, follicular selection and maturation, fertilization, and the recognition and maintenance of pregnancy. The pharmacological and therapeutic potential may be limited, as the ovarian adnexa are relatively difficult to access. Instillation of hormones into the uterine lumen will probably induce a higher plasma concentration in the ovarian arterial blood than in peripheral arterial plasma. A culdoscopic or endoscopic approach might permit introduction of long-acting depots in the uterine fundus near the Fallopian tubes and/or ovaries.     

Studies on the influence of gonadotrophin levels in the early follicular phase on the ovarian response to stimulation

The gonadotrophic regulation of folliculogenesis has been extensively investigated but little attention has been paid to the influence of early follicular phase levels of endogenous FSH and the FSH/LH ratio when planning ovulation stimulation therapy for IVF. The influence of these factors was investigated in the three studies reported in this paper. A fixed schedule of ovulation stimulation therapy which employed standard treatment regimens, irrespective of the ovarian response, was used to eliminate variation due to treatment factors. Cycles were pretreated with an oestrogen-progestogen contraceptive pill or a progestogen (norethisterone). It was found that both oestrogen-progestogen and progestogen alone decreased the plasma FSH level, although the FSH/LH ratio was significantly reduced only by oestrogen-progestogens. In clinical IVF studies, oestrogen-progestogen pretreatment was associated with a significant reduction in the preovulatory concentration of oestradiol in plasma and the number of aspirated follicles, compared to norethisterone. The administration of FSH for 2 days following oestrogen-progestogen pretreatment and prior to the fixed schedule of ovulation stimulation normalized ovarian steroidogenesis and follicular development. Early follicular phase supplementation with FSH had no influence on progestogen pretreated cycles. The final experiment investigated the influence of FSH/LH levels in the early follicular phase on the outcome of ovarian stimulation. The preovulatory oestradiol concentration was reduced when baseline FSH/LH levels were low compared with when these values were high. Administration of FSH for 2 days in the early follicular phase improved the preovulatory level of oestradiol when baseline FSH/LH was low but had no effect when baseline FSH/LH levels were high.(ABSTRACT TRUNCATED AT 250 WORDS)     

Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in the absence of secretory changes

BACKGROUND: Ovarian stimulation for IVF profoundly alters the early luteal phase endometrial development. It has been hypothesized that this process has already started in the late follicular phase, as the endometrium has already been exposed to high steroid concentrations since that phase. The aim of the present study was to prospectively investigate the effect of multi-follicular ovarian stimulation for IVF on the late follicular phase endometrium histology and the expression of estrogen receptor (ER) and progesterone receptor (PR). METHODS: In a cross-over study, 11 infertile women with normal ovulatory function, participating in an IVF programme and treated with GnRH antagonist/recombinant FSH ovarian stimulation, were enrolled in the study. Endometrial biopsies were taken in a natural cycle on the day of the onset of the surge of the LH, and in a subsequent stimulation cycle on the day of hCG administration for final oocyte maturation. Endometrial histological dating was carried out according to Noyes' criteria. Immunohistochemistry was performed, using commercially available antibodies for ER and PR endometrial expression. The immunohistochemical signal was recorded in 1000 epithelial cells in each compartment (glands and stroma). Endometrial expression for each of the two receptors was graded on a scale of 0-3, based on the intensity of nuclear staining. Then a score range between 0 and 3000 was recorded, and expressed as a mean score per 1000 stroma or glandular cells per sample (range: 0-3). RESULTS: Histological examination of biopsies both in natural and stimulated cycles showed no secretory changes. However, in stimulated cycles, PR expression was significantly up-regulated compared to natural cycles in both glands (1.67 versus 1.34, P < 0.05) and stroma (1.98 versus 1.62, P < 0.05), whereas ER was down-regulated in glands (1.15 versus 1.43, P < 0.05). In IVF cycles, the progesterone measurements, although within normal values (range 0.8-1.4 microg/l), were significantly higher than in natural cycles (0.99 vs 0.63 microg/l, respectively, P = 0.008). An ongoing pregnancy rate of 37.5% was achieved in the stimulated cycles. DISCUSSION: Although the current study found no early secretory transformation in stimulated endometria before hCG administration, the ER and PR expression in these endometria is similar to the one described during the first days of the luteal phase in natural cycles. Supraphysiological concentrations of estradiol and subtle progesterone rises in the late follicular phase might be responsible for this modulated steroid receptor profile. This phenomenon indicates accentuated maturation of the endometrium in IVF cycles from the pre-ovulatory phase onwards.     

Suppression of prolactin secretion during ovarian hyperstimulation is followed by elevated serum levels of endometrial protein PP14 in the late luteal phase

A double-blind placebo-controlled study on bromocriptine administrationduring days 2-12 of ovarian hyperstimulation for in-vitrofertilization(IVF) showed that, in bromocriptine cycles, levels of the endometrialprotein PP14 were higher in the late luteal phase. This wasverified both by calculating forward from the day of human chorionicgonadotrophin (HCG) administration and backward from the onsetof the next period. Bromocriptine had no effect on IVF performance.During bromocriptine treatment the serum prolactin levels declinedand serum oestradiol levels were higher on day 9 of the cycle.There was a positive correlation (r =0.55; P = 0.012) betweenthe serum oestradiol levels on day 9 and the PP14 levels ondays 22-23 of the cycle. No difference was found in the lutealphase progesterone levels between bromocriptine-and placebo-treatedcycles. These results suggest that low prolactin and/or highoestradiol levels during the follicular phase have an influenceon the subsequent secretory capacity of the endometrium as reflectedby secretion of a specific endometrial protein     

Diagnostic techniques: Blood flow changes in uterine and ovarian vasculature, and predictive value of transvaginal pulsed colour Doppler ultrasonography in an in-vitro fertilization programme

The role of transvaginal pulsed colour Doppler ultrasound inthe prediction of the outcome of in-vitro fertilization (IVF)therapy was assessed longitudinally in 30 patients during stimulatedcycles. The pulsatility index (PI) of the uterine arteries didnot change significantly until the mid-luteal phase. Within6 days after the beginning of stimulation the maximum peak systolicvelocity of the uterine blood flow had increased significantlyfrom 27.6 ± 8.9 to 36 ± 12.8 cm/s. No differencewas found in uterine PI between pregnant and non-pregnant women.The PI of intra-ovarian flow was also similar in both groups.However, there was an insignificant increase in uterine receptivitywhen the PI of the uterine artery was between 2.0 and 2.99 onthe day of embryo transfer. Nevertheless, the appraisal of theprognostic outcome of the treatment could not be made with Doppler.     

The influence of Sildenafil citrate on uterine tissue perfusion and the cardiovascular system during the luteal phase of the ovarian cycle in cows

The aim of the study was to evaluate the influence of the Sildenafil citrate on the blood flow in the uterus of cows during dioestrus. Uterine blood flow was examined in five, healthy, adult cows. Between day 6–8 of the ovarian cycle, each cow received 200 mg of sildenafil diluted in 10 ml of warm saline into the body of the uterus. Analysis of the blood pressure, ECG and the maximum velocity in m/s (V max) in the aorta was performed and selected parameters of the blood flow (PI, pulsatile index; RI, resistance index; SPV, systolic peak velocity; EDV, end diastolic velocity; FVI, flow velocity integral; SV/DV, systolic peak velocity: end-diastolic velocity ratio) were measured in the uterine artery (Arteria uterine) before and after sildenafil infusion. In addition, Color Doppler examination of the uterine wall perfusion was analyzed. A significant decrease of values of PI and SV/DV ratio as well as an increase of end diastolic velocity and time averaged maximum velocity was noted. With the use of color coded sonography, the increased intensity of the blood flow in the uterine wall was observed. It was concluded that intrauterine administration of sildenafil during dioestrus can increase uterine tissue perfusion.     

The excess in 2-5 mm follicles seen at ovarian ultrasonography is tightly associated to the follicular arrest of the polycystic ovary syndrome

BACKGROUND: We previously hypothesized that the excess of 2–5 mmfollicles seen at ovarian ultrasonography might be involvedin the follicular arrest (FA) of polycystic ovary syndrome (PCOS),independently from the main putative contributors of FA, namelyhyperandrogenism and hyperinsulinism. METHODS: A multivariate statistical analysis was applied retrospectivelyto clinical, biological and ultrasound data that were consecutivelycollected during 5 years in 457 patients with polycystic ovariesand in 188 age-matched non-hyperandrogenic and regularly cyclingcontrols without PCO at ultrasound. RESULTS: Stepwise discriminant analysis indicated that in PCOS the 2–5 mmfollicle number (FN) gave the strongest correlation to severityof the FA, followed by age and then by fasting insulin level.The other variables [waist circumference (WC), 6–9 mmFN, serum testosterone, FSH, LH and ovarian area] were rejectedby the analysis. Multiple linear regression indicated a significantand independent negative relationship between the 2–5and 6–9 mm FN in the PCOS (r = – 0.186, P <0.01) and control groups (r = – 0.281, P < 0.01). InPCOS only, the 6–9 mm FN was negatively and independentlyrelated to the WC (r = – 0.108, P < 0.05). CONCLUSIONS: The size of the 2–5 mm follicle pool is an independentand important contributor to the FA of PCOS. This result couldbe explained by an exaggerated physiological inhibitory effectfrom this pool on the terminal follicle growth. The metabolicderangement of PCOS that also contributes to the FA would actthrough a different mechanism.     

成年家犬胸腰段脊髓营养动脉的解剖学研究

目的 :了解成年家犬胸腰段脊髓营养动脉的数目、管径和配布特点。方法 :7只成年家犬动脉灌注乳胶后取脊髓全长 ,对其胸腰段脊髓营养动脉进行观测。结果 :胸腰段脊髓的前根髓动脉 (12 .6± 2 .1)条 ,管径 (0 .2 182± 0 .0 773 )mm ,基本不成对分布 ,左侧者居多 ;最大前根髓动脉位于中腰髓 ,管径 (0 .3 83 6± 0 .0 3 3 1)mm ,动脉干长 (9.17± 1.68)mm。胸腰段脊髓后根髓动脉数目 (12 .7± 3 .4)条 ,管径 (0 .1663± 0 .0 3 72 )mm ,多不成对分布。前正中动脉在胸髓较细 ,管径为 (0 .14 68± 0 .0 2 5 2 )mm ,在腰髓较粗 ,管径为 (0 .2 677± 0 .0 414 )mm。两条后外侧动脉均较细 ,其间多吻合。结论 :与人类不同 ,成年家犬胸腰段脊髓动脉血供相当丰富 ,以犬为实验动物 ,制作急性脊髓缺血损伤模型时必须考虑到被阻断血流动脉的级别、节段、侧别、数目等因素对局部脊髓血供的影响。     

Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF

Endometrial growth is thought to depend on uterine artery blood flow and the importance of endometrial development on in-vitro fertilization (IVF) outcome has been previously reported. Nitric oxide (NO) relaxes vascular smooth muscle through a cGMP-mediated pathway and NO synthase isoforms have been identified in the uterus. Sildenafil citrate (Viagra), a type 5-specific phosphodiesterase inhibitor, augments the vasodilatory effects of NO by preventing the degradation of cGMP. In this preliminary report we describe the use of vaginal sildenafil to improve uterine artery blood flow and sonographic endometrial appearance in four patients with prior failed assisted reproductive cycles due to poor endometrial response. The uterine artery pulsatility index (PI) was measured in a mock cycle after pituitary down-regulation with Lupron. The PI was decreased after 7 days of sildenafil (indicating increased blood flow) and returned to baseline following treatment with placebo. The combination of sildenafil and oestradiol valerate improved blood flow and endometrial thickness in all patients. These findings were reproduced in an ensuing gonadotrophin-stimulated cycle. Three of the four patients conceived. Although greater numbers of patients and randomized evaluation are needed to validate this treatment, vaginal sildenafil may be effective for improving uterine artery blood flow and endometrial development in IVF patients with prior poor endometrial response.     

Value of serum and follicular fluid cytokine profile in the prediction of moderate to severe ovarian hyperstimulation syndrome

The aim of this study was to examine the role of serum and follicular fluid pro-inflammatory cytokines and vascular endothelial growth factor (VEGF) in the prediction of ovarian hyperstimulation syndrome (OHSS). A total of 156 consecutive women undergoing in-vitro fertilization were recruited. The study group comprised 12 women who subsequently developed moderate (n = 7) or severe (n = 5) OHSS. The two control groups were comprised of a randomized selection of 12 high-risk and 12 low-risk women in whom OHSS did not develop. Serum was collected on days of human chorionic gonadotrophin, oocyte retrieval, and embryo transfer. Serum and follicular fluid concentrations of interleukin (IL)-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), and VEGF were measured. Follicular fluid IL-6 concentrations at the time of oocyte retrieval and serum IL-8 concentrations at the time of embryo transfer were significantly higher in the OHSS compared to the two control groups (P = 0.026 and P = 0.017 respectively). Serum concentrations of TNF-alpha and VEGF showed no statistically significant difference between the OHSS group and the controls at any studied time point. This study suggests that follicular fluid IL-6 concentrations at the time of oocyte retrieval and serum IL-8 concentrations on the day of embryo transfer may serve as early predictors for this syndrome.     

Serum levels of free androstenedione, testosterone and oestradiol are lower in the follicular phase of conceptional than of non-conceptional cycles after ovarian stimulation with a gonadotrophin-releasing hormone agonist protocol.

Serum concentrations of total and free androstenedione, testosterone and oestradiol were followed during the follicular phase in women undergoing ovarian stimulation for treatment by in-vitro fertilization and embryo transfer (IVF-ET) and compared to those in natural unstimulated cycles. In addition, 10 conceptional and 18 non-conceptional cycles were compared in an attempt to understand the background for successful IVF cycles. The ultra-short gonadotrophin-releasing hormone agonist protocol was used for ovarian stimulation. Throughout the follicular phase, levels of total and free androstenedione and oestradiol were significantly lower in conceptional than in non-conceptional IVF cycles. In addition, levels of free testosterone during the follicular phase were significantly lower in women who conceived compared to non-conceptional IVF cycles, whereas levels of total testosterone were similar. Levels of both free and total androstenedione increased significantly from the second day of the menstrual cycle until oocyte retrieval in non-conceptional IVF cycles, whereas levels in conceptional IVF cycles and unstimulated cycles showed no increase. On the day of oocyte retrieval levels of free and total androstenedione were significantly higher in non-conceptional IVF cycles than in conceptional IVF cycles and unstimulated cycles, which were similar. This study suggests that appropriate levels of free biologically active androgens and oestradiol are important parameters for successful conception.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of the ovarian volume, number and volume of follicles and ovarian vascularity by three-dimensional ultrasonography and power Doppler angiography on the HCG day to predict the outcome in IVF/ICSI cycles

OBJECTIVE: The aim of this prospective study was to investigate whether ovarian blood flow is related to embryological parameters and whether it could be a predictor of outcomes of IVF/ICSI. METHODS: Eighty infertile women underwent ovarian stimulation with gonadotrophins after a long protocol with GnRH agonists. The ovarian volume (OV), number of follicles (NF) and follicular volume (FV) of all follicles >10 mm and vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) were obtained by three-dimensional (3D) ultrasonography and power Doppler angiography (PDA) on the day of HCG administration. These parameters were tested for their relation with IVF laboratory parameters. RESULTS: The OV, FV, VI, FI and VFI were significantly greater in the pregnant group. The NF and FV were the only independent predictors of the number of oocytes retrieved, mature and fertilized, and the number of embryos developed and their cumulative embryo score. Nevertheless, the number of grade 1 embryos depends on the NF and the VI. The ovarian FI and the number of transferred grade 1 embryos can predict gestation in 76% of IVF patients. A low FI and non-grade 1 embryo transferred are also associated with an increased pregnancy loss. CONCLUSION: 3D ultrasonography and PDA allow for an easier ovarian assessment in IVF cycles. The predictive value of IVF outcome suggests a high clinical usefulness of this new technique.