Reduced in-vitro fertilization of human oocytes from patients with raised basal luteinizing hormone levels during the follicular phase

A series of 62 women were managed in the University of Western Australia/PIVET Laboratory in-vitro fertilization programme. In 60 of them follicle growth was stimulated with clomiphene citrate with or without additional human menopausal gonadotrophin (hMG) and in two with hMG alone. Follicles were aspirated at laparoscopy following an hCG trigger injection and occasionally following a spontaneous luteinizing hormone (LH) surge. Oocytes were inseminated with 0.5 X 10(5)-10(5) sperm/ml 3-6 h later. A significant reduction (P less than 0.001) in the fertilization rate of mature oocytes was observed in those patients whose basal serum LH values were greater than 1 SD above the mean. Fifty-nine women subsequently had embryo transfer and of 10 clinical pregnancies, none occurred in those with elevated LH values. Reduced fertilization may be a reflection of premature oocyte maturation or ageing. This may have clinical implications in the management of some patients with unexplained infertility.     

Follicular fluid α1-antitrypsin—correlation with fertilizing capacity of oocytes

Summary. Follicular fluid and serum concentrations of α-antitrypsin (α₁-AT) were determined by radial immunodiffusion in 72 samples obtained from 33 infertile women undergoing in-vitro fertilization and embryo transfer. A statistically significantly lower concentration of α₁-AT was found in follicular fluids from which mature oocytes were recovered (mean 1.52, SE 0.06 g/l) than in those yielding immature oocytes (mean 2·96, SE 0·22 g/l). There was also a significantly higher rate of fertilization (85%) for oocytes from follicular fluids with α₁-AT concentrations of ≤2·0 g/l than for those obtained when the α₁-AT concentration was >2·0 g/l (only 25%). The mean follicular fluid α₁-AT concentration (1 ·52, SE 0·06 g/l) of follicles yielding mature oocytes was significantly lower than the relevant mean serum concentration (3·17, SE 0·10 g/l). There was, however, no significant difference between follicular and serum concentration of α₁-AT in the group yielding immature oocytes or in the serum concentrations between the different oocyte maturity groups. The measurement of follicular α₁-AT may be a useful adjunct in predicting which oocytes are mature and likely to be fertilized.     

Prostaglandin E production by amniotic cells in relation to term and preterm labour

Summary. The rate of prostaglandin E (PGE) production was measured in collagenase-dispersed amniotic cells obtained from 14 women after spontaneous labour at term—seven after spontaneous preterm labour, nine after delivery by elective caesarean section at term and six after induction of labour at term. Cells were incubated with and without arachidonic acid and PGE was estimated by specific radioimmunoassay. Basal PGE output (pmol/10⁶ cells per 3 h) was highest in the spontaneous labour group, 27·5 (SEM 5·5) and lowest in the preterm labour group, 4 (SEM 1·2) ( P <0·001). Values in the elective section and induction groups were 13·6 (SEM 2·7) and 10 (SEM 3·1), respectively; these values were significantly higher than in the preterm labour group and the values after induction were significantly lower than after spontaneous labour. Addition of arachidonic acid resulted in a significant increase in PGE output in all groups, but the values after preterm labour remained significantly lower than those of any group at term. These data indicate that towards term there is a maturation in the PG synthetase activity of the amnion and that PGE output in this tissue is increased in spontaneous labour.     

Short-term reproductive prognosis when no cause can be found for recurrent miscarriage

Summary. The short-term reproductive prognosis of recurrent miscarriage for which no cause was found has been evaluated in 95 couples investigated between 1980 and 1986 at the First Obstetric and Gynaecological Clinic of the University of Milan. The actuarial overall 3-year livebirth delivery rate was 64%, increasing constantly with time. The reproductive success rate decreased with the number of previous miscarriages from 80% in women with two, to 60% with three and 46% with four or more miscarriages. No effect of age and socio-economic status emerged. There was a positive association between the number of previous miscarriages and the risk of miscarriage in the next pregnancy. Compared with women with two miscarriages the relative risk of another miscarriage was 2·3 for those with three previous miscarriages and 5·0 for those with four or more (χ²₁ for trend adjusted for age = 5·2, P = 0·02).     

Cigarette smoking in pregnancy results in marked decrease in maternal hCG and oestradiol levels

Summary. We have examined serum levels of oestradiol (E₂), sexhormone binding globulin (SHBG) and human chorionic gonadotrophin (hCG) during early pregnancy in relation to smoking status at the time of sampling in a series of 147 women. Smoking was associated with significantly depressed serum levels of E₂, SHBG and hCG: in smokers, E₂ levels were on average 17·6% lower ( P =0·037), SHBG levels were 12·4% lower ( P =0·15), and hCG levels were 21·5% lower ( P =0·044). There appeared to be a steady decline in these values with increasing cigarette consumption. These lower hormone levels in smokers may explain certain adverse effects of smoking in pregnancy.     

Amerlex free triiodothyronine and free thyroxine levels in normal pregnancy

Summary. Free triiodothyronine (FT₃) and free thyroxine (FT₄) were measured in 159 women during normal pregnancy and compared with non-pregnancy reference ranges for these hormones. FT₃ values fell from the reference level of 6·34 (SD 1·06) pmol/l to 3·87 (SD 0·54) pmol/l in the 3rd trimester; corresponding figures for FT₄ were: reference 16·92 (SD 2·97) pmol/l, 3rd trimester 11·29 (SD 2·01) pmol/l. There were no significant changes in the 1st trimester; 4% and 69% of FT₃ results in the 2nd and 3rd trimesters respectively fell below the reference range of mean ±2 SD. The corresponding findings for FT₄ were 4% and 42%. FT₃ correlated reasonably well with total T₃ ( r =0·90) and was acceptably precise (within-batch CV 2·1% at 5·6 pmol/l, between-batch CV between 3·1% and 4·7% at six levels).     

The serum pregnancy-specific β1-glycoprotein to betahuman chorionic gonadotrophin ratio as an index of prognosis in patients with choriocarcinoma

Summary. The ratio of serum pregnancy-specific β₁-glycoprotein (SP1) to the β-subunit of human chorionic gonadotrophin (β-hCG) before and after chemotherapy was measured in 12 patients with metastatic choriocarcinoma. The ratios before chemotherapy ranged between 0^.03 and 0^.75, with a mean value of 0^.34 (SD 0^.21). The ratio increased to over 1^.0 (1^.05–53^.3) after one or two courses of chemotherapy in seven of the 12 patients. These women achieved complete remission. In the other five patients who died of the disease due to drug resistance of the tumour, the ratio after chemotherapy was low (0^.04–0^.74) and tended to decline. These data suggest that the serum SPl/β-hCG ratio can be used to predict the prognosis of patients with choriocarcinoma.     

Assessment of pituitary secretory capacity in women with hypogonadotrophic hypogonadism by using a long-acting synthetic analogue of luteinizing hormone releasing factoi

Summary. The gonadotrophin responses to single and repeated injections of a long-acting synthetic analogue of luteinizing hormone releasing factor (LRF), d -Ser(TBU)⁶EA¹⁰LHRH, were investigated in 10 women with normoprolactinaemic hypogonadotrophic hypogonadism. Abnormal luteinizing hormone (LH) responses were observed in two of the five patients treated with 5μg of the analogue and in all five patients treated with three injections of 10, 20 and 10 uμg administered at intervals of 10-14 h. However, the LH response to repeated injections of the analogue was of similar magnitude and duration to that observed in normal women in response to an oestrogen provocation test in the early-to-mid follicular phase of the cycle. Thus failure of the LH response to oestrogen provocation in women with hypogonadotrophism results from hypothalamic rather than primary pituitary dysfunction. This study confirms the usefulness of this analogue of LRF in the assessment of pituitary secretory function in women with abnormal responses to oestrogen positive feedback.     

Platelet angiotensin II binding sites in normotensive and hypertensive women

Summary. Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10⁹ cells) when compared with the non-pregnant women (9.0 fmol/10⁹ cells   P <0.001  ). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10⁹ cells) when compared with the 25 normotensive pregnant women (   P <0.001  ). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10⁹ cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10⁹ cells) although the difference was not statistically significant (   P <0.04  ). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy.     

Studies on the effects of nitrendipine on oxytocin-angiotensin II- and ergometrine-induced contraction of pregnant human myometrium in vitro

Summary. Calcium channel blockers inhibit myometrial contractility by preventing the increase in intracellular free calcium which follows stimulation. They could thus be useful in treating premature labour. The effect of nitrendipine, a dihydropyridine calcium channel antagonist, on the contractile response of strips of pregnant human myometrium to oxytocin, angiotensin II (All) and crgomctrinc has been examined. A total of 68 tissue strips were studied, with random allocation to treatment group. Initial concentration: response curves to one of the three agonists were determined; the concentration: response determinations were repeated in the presence or absence of nitrendipine at 10⁻⁹M. The initial EC₅₀s for tissues exposed to oxytocin and All were 8·2xlO⁻¹⁰M and 3·4x10 ⁸m respectively. The contractile response to both agonists was significantly blunted in the presence of nitrendipine (ANOVA; P <0·001 for both agents). This effect was greatest at high agonist concentrations. The initial EC₅₀s for tissues exposed to ergometrine was 3·9xlO⁻⁸M. Exposure to nitrendipine blunted the response (ANOVA; P <0·001), an effect most marked at low concentrations of ergometrine. The effect of nitrendipine on myometrial responses to the naturally occurring hormones oxytocin and All supports suggestions of a role for it in inhibiting premature labour.     

Do raised serum luteinizing hormone levels during stimulation for in-vitro fertilization predict outcome?

Previous reports associating raised LH concentrations with reduced fertilization and pregnancy rates in women undergoing in-vitro fertilization (IVF) have assumed a Gaussian distribution of LH values with IVF treatment. We have determined the serum LH range during ovarian stimulation for IVF with a single regimen of clomiphene citrate/hMG from 102 consecutive IVF conception cycles. The results show a non-Gaussian distribution of LH values. Application of this LH range to a consecutive series of 596 women undergoing IVF treated with this single regimen showed no difference in pregnancy rates, fertilization rates, median number of oocytes fertilized or retrieved when analysed with respect to serum LH concentrations above the 75th or 95th centile for greater than or equal to 3 days of an IVF treatment cycle. We conclude that follicular-phase LH concentrations do not predict IVF fertilization rates or clinical outcome and are not clinically useful in individual patient management.     

Are leukotrienes involved in human uterine contractility?

Summary. The effects of leukotrienes (LT) on the contractility of human and rat myometrial strips in vitro were compared with the effects of prostaglandins (PGs) and oxytocin. Preparations of human myometrial membranes were investigated for the presence and characteristics of LTC₄ receptors. Neither the peptido-leukotrienes (LTC₄, LTD₄, LTE₄) nor LTB₄ had any consistent effect, stimulatory or inhibitory, on human pregnant or non-pregnant myometrium, at doses up to 1·25 μM; nor did they have any effect in rat non-pregnant myometrium. As expected, PGE₂, PGF_2α (0·3 μM) and oxytocin (5 nM) stimulated human pregnant myometrium. PGF_2α stimulated and PGE₂ inhibited human non-pregnant myometrium but oxytocin had no effect; all three compounds stimulated rat non-pregnant myometrium. The binding of ³H-LTC₄ to human myometrium was specific (LTC₄> LTD₄ >>> LTE₄, LTB₄, PGE₂, PGF_2α, arachidonic acid) but of low affinity compared with the binding of ³H-PGE₂ to the same membrane preparations. These data support the view that leukotrienes have little direct influence on myometrial contractility.     

The relation between vaginal pH and the microbiological status in vaginitis

Summary. The vaginal pH, microbial flora and presence of clue cells were investigated in 89 women who were seen a t a sexually transmitted diseases clinic with a vaginal discharge or because they were contacts of men with gonococcal or non-gonococcal urethritis or because they were seeking a routine examination. None of the women had received antibiotics for at least 4 weeks before examination. A clinically normal vaginal secretion was found in 21 (55%) of 38 women who had a vaginal pH of 5.0–5.5. while such a secretion was found in only 7 (14%) of 51 women who had a pH value of 6·0–7·5. Clue cells, Chlatmydia trachomatis and Mycoplasrna hominis were found two to three times more often in women with the higher pH value than in those with the lower value and Ureaplasma urealyticum and Trichomonas vaginalis also occurred more frequently in the former group. Furthermore. large numbers of M. hominis organisms ( 10⁶colour changing units/ml) were associated significantly with the higher pH value. However, there was no appreciable difference in the distribution of Candida albicans between the two groups. C. trachomatis but not the other micro-organisms was isolated most often from women who were taking oral contraceptives. The results indicate that a pH of 2.6.0 is strongly predictive of infection and may be more useful than the type of discharge in suggesting a need for confirmatory microbiological tests.     

Paclitaxel in combination with cisplatin is less effective for peripheral blood progenitor cell mobilization

Abstract. Kurata H, Takakuwa K, Tsuneki I, Aoki Y, Tanaka K. Paclitaxel in combination with cisplatin is less effective for peripheral blood progenitor cell mobilization.
The purpose of this study was to determine the efficacy of paclitaxel in combination with cisplatin and granulocyte-colony stimulating factor (G-CSF) for mobilization of peripheral blood progenitor cells (PBPC). Twenty-seven patients with gynecological cancer received paclitaxel and cisplatin (TP, n = 9) or other platinum-based chemotherapy ( n = 18) (etoposide and cisplatin [ n = 5]; cyclophosphamide, adriamycin, and cisplatin [ n = 8]; or pepleomycin, etoposide, and cysplatin [ n = 5]). Each combination was followed by G-CSF. The mean number of colony-forming unit granulocyte macrophage (CFU-GM)/kg and CD34⁺ cells/kg collected per cycle was 1.2 × 10⁵ and 0.8 × 10⁶ after the TP regimen, compared with 2.6 × 10⁵ ( P < 0.05) and 2.0 × 10⁶ for patients who received other platinum-based chemotherapy. The CFU-GM target yield (≥1.0 × 10⁵/kg) was achieved in 56% and 83% patients in the TP and comparison group, respectively. With the TP regimen, a younger age (≤50 years of age) and fewer prior chemotherapy cycles (≤2) were associated with the CFU-GM targeted yield (<0.05). In conclusion, TP mobilized PBPC less effectively than other platinum-based chemotherapy. Therefore, the TP regimen may need to be changed to another appropriate regimen when PBPC mobilization is planned for high-dose chemotherapy in gynecological cancer patients.     

The role of luteinizing hormone in folliculogenesis and ovulation induction

OBJECTIVE: To review the physiologic, pathophysiologic, and clinical roles of LH in follicle and oocyte development and maturation and to assess the effects of LH content in exogenous gonadotropin preparations used for ovulation induction. DESIGN: Critical review of the scientific literature devoted to folliculogenesis. Evaluation of comparison studies that used different gonadotropin preparations for ovulation induction. CONCLUSION(S): Folliculogenesis and oocyte maturation are complex processes that require the action of both LH and FSH. Luteinizing hormone is essential to provide the androgen substrate for estrogen synthesis, which in turn contributes to oocyte maturation and may play a relevant role in optimizing fertilization and embryo quality. Although the excessive LH secretion that is present in some disorders is detrimental to reproductive function, this is not applicable to ovulation induction with hMG because this menotropin does not increase daily plasma LH levels. The results of ovulation induction with hMG or FSH-only regimens did not differ in studies conducted in patients with polycystic ovary syndrome and in most studies conducted in ovulatory women undergoing assisted reproductive techniques; conversely, hMG was clearly superior to purified FSH for the treatment of hypogonadotropic hypogonadism. Miscarriage rates were not affected by the use of hMG. Thus, low but detectable LH concentrations positively influence the outcome of ovulation induction in patients with ovulatory disorders and women undergoing assisted reproductive techniques.     

Urinary oestrogen levels and follicle ultrasound measurements in clomiphene induced cycles with an endogenous luteinizing hormone surge

Summary. Total oestrogen in urine and the ultrasonic size of the follicles were measured in relation to the onset of the endogenous luteinizing hormone (LH) surge (day 0) in 18 cycles induced with clomiphene citrate in an in-vitro fertilization programme. Oestrogen values in urine (μg/24 h) increased progressively during the late follicular phase up to the day of the onset of the surge. The mean maximum follicle diameter (22·3, SD 4·7 mm) estimated by ultrasound was measured on day 0. At the onset of the LH surge, the values of urinary total oestrogen showed a better relation with the total volume of the first three follicles in order estimated by ultrasound ( r = 0·71) than with the mean ultrasonic diameter of the leading follicle ( r = 0·56). A wide range of individual values for both urinary oestrogen and follicle size was found. In another group of 32 women treated with clomiphene for recovery of oocytes used for research purposes, a good correlation was found between the mean ultrasonic follicle diameter 16 h before the laparoscopy and the follicle diameter calculated from the fluid volume at aspiration ( r = 0·80). These results suggest that the decision when to give human chorionic gonadotrophin (hCG) in an in-vitro fertilization programme remains arbitrary in many individual cases. Apart from the oestrogen levels, the calculation of the size of all follicles, instead of only the leading one, may give further help in timing the hCG.     

Prognostic significance of raised serum α-fetoprotein levels in twin pregnancies

Summary. Maternal serum α-fetoprotein (AFP) was measured during the second trimester in 219 twin pregnancies uncomplicated by neural-tube defects (NTD) and in 11 twin pregnancies discordant for NTD. Serum AFP levels were recorded in multiples of the median value (MOM) calculated from normal singleton pregnancies. Of the twin pregnancies uncomplicated by NTD 49% had AFP levels <2·5 MOM, 7·8% had levels >5 MOM and 59% of these were associated with either abortion, stillbirth or fetus papyraceous. In twin pregnancies with serum AFP levels <5 MOM an unsuccessful outcome was noted in only 4% (χ², P <0·05). There was a significant negative correlation between serum AFP levels and combined birthweights (r=0·954). All 11 pregnancies discordant for NTD had serum AFP values >5 MOM and this level appears to be a suitable cut-off point above which there should be further diagnostic investigations and monitoring of fetal well-being.     

控制性超促排卵过程中血清LH低于正常时添加rLH或hMG的效果比较

目的:比较控制性超促排卵(COH)过程中血清促黄体生成素(LH)低于正常时添加基因重组LH(rLH)或人绝经期尿促性腺激素(hMG)的效果。方法:选取因输卵管因素不孕行常规IVF-ET患者85例,全部采用长方案超促排卵,均给予基因重组促卵泡激素(rFSH)进行超促排卵,超促排卵第6日时如血清LH≥1.2 mIU/ml,继续用rFSH,作为对照组(rFSH组,n=37);如血清LH<1.2 mIU/ml,则随机纳入到hMG组(rFSH+hMG,n=30)或rLH组(rFSH+rLH,n=18)。结果:3组间在促性腺激素(Gn)用量、COH天数、获卵数、双原核率、优质胚胎率、临床妊娠率方面均无统计学差异。hMG组的rFSH用量显著低于rLH组(P<0.01)。结论:在黄体期降调节长方案超促排卵第6日,如血清LH<1.2 mIU/ml时,添加hMG或rLH,可获得与对照组(rFSH组)相似的临床结果。与添加rLH组相比,添加hMG组降低了rFSH用量,减少了患者的费用。     

Haematological Effects of Betamethasone Treatment in Late Pregnancy

Summary: To assess the maternal haematological effects of betamethasone administered in late pregnancy, an automated full blood count was performed before and daily for 5 days after betamethasone in 25 women with a singleton pregnancy between 23 and 33 weeks' gestation. From a mean (±SD) baseline level of 11.0 ± 2.2 ± 10⁹/L, the total white cell count increased significantly to 13.2 ± 2.9 ± 10⁹/L and 13.5 ± 3.1 ± 10⁹/L on the first and second day after treatment respectively, returning to baseline on day 3 (p < 0.0001, ANOVA). These changes represented a mean increase in the neutrophil count of 35% and a mean decrease in the lymphocyte count of 23%. While there was considerable intersubject variation in the extent of the changes, this study has quantified the leucocytosis induced by betamethasone in late pregnancy, information that may assist with the clinical evaluation of a woman at risk of preterm delivery.     

Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate

The relationship of the circulating level of progesterone (P) on the day of human chorionic gonadotropin (hCG) injection to occurrence of clinical pregnancy was examined in 133 leuprolide acetate human menopausal gonadotropin (hMG) in vitro fertilization cycles in women having at least three embryos transferred. Progesterone concentrations greater than 0.5 ng/mL were associated with a significantly lower rate of pregnancy (12/59, 20%) compared with less than 0.5 ng/mL (40/74, 54%, P less than 0.005). The higher P cycles were associated with greater patient age and hMG dose, although these relationships appeared to be indirect. Luteinizing hormone (LH) concentrations remained suppressed. Ovarian stimulation may cause excessive luteinization and an adverse cycle outcome even in the presence of low LH levels. Prospective use of P levels may be helpful to determine optimal hCG timing.