Pregnancy: Corpus luteum failure in ectopic pregnancy

The endocrinology of ectopic pregnancy was studied in orderto investigate the origin of the discordance in the circulatingamounts of human chorionic gonadotrophin (HCG) and those ofoestradiol and progesterone. Serial maternal blood samples wereobtained at 4–9 weeks gestation from 93 patients who becamepregnant following in-vitro fertilization and embryo transferincluding 10 ectopic, 21 anembryonic and 62 normal singletonpregnancies. The samples were analysed for HCG, Schwangerschaftprotein-1 (SP-1), pregnancy-associated plasma protein-A (PAPP-A),progesterone and oestradiol. In ectopic pregnancies, concentrationsof all substances analysed were significantly reduced comparedto singleton pregnancies from 5 weeks gestation (P < 0.05–0.001)but they were not significantly different from those of anembryonicpregnancies. In ectopic pregnancies, associations were foundbetween the concentration of both HCG and SP-1 and those ofprogesterone and oestradiol. No associations were found betweenPAPP-A and any other substances analysed. This may be due toinsensitivity of the PAPP-A assay; alternatively PAPP-A concentrationsmay be differentially reduced in ectopic pregnancy. These findingssuggest that progesterone and oestradiol are derived from thecorpus luteum in early ectopic pregnancy but that the corpusluteum fails rapidly and the dominant source of both hormonesbecomes the trophoblast as early as 5 weeks.     

Paired human chorionic gonadotrophin determinations for the prediction of pregnancy outcome in assisted reproduction

The aim of this study was to determine the prognostic value of single and paired measurements of serum concentrations of human chorionic gonadotrophin (HCG) for successful pregnancy following in-vitro fertilization (IVF) and tubal embryo transfer (TET). We analysed serum HCG concentrations 15 and 22 days after IVF or TET in 198 conception cycles. Cut-off values of serum HCG were determined by a receiver operating characteristic (ROC) curve. On the basis of single HCG samples on day 15 (HCG15) after transfer, using a cut-off value of HCG15 = 150 mIU/ml, the sensitivity was 71% and the specificity was 77%. The positive predictive value (HCG15 > or = 150 mIU/ml indicating a normal pregnancy) was 89%, while the negative predictive rate (HCG15 < 150 mIU/ml indicating an abnormal pregnancy) was 51%. Patients with HCG15 < 150 mIU/ml but HCG22/HCG15 ratio > or = 15, still had a 90% chance of normal pregnancy. However, in patients with HCG15 < 150 mIU/ml and an HCG22/HCG15 ratio < 15, there was an 84% chance of an abnormal pregnancy. We conclude that a single HCG15 determination combined with the ratio of HCG22 to HCG15 has a higher diagnostic accuracy for prediction of pregnancy outcome than either analysis alone.      

Pregnancy: Reduced circulating placental protein concentrations during the first trimester are associated with preterm labour and low birth weight

Serum concentrations of human chorionic gonadotrophin (HCG),Schwangerschaftsprotein 1 (SP-1), pregnancy-associated plasmaprotein A (PAPP-A), progesterone and oestradiol were measuredat weekly intervals between the fifth (embryo transfer plus3 weeks) and 13th week of gestation during the first trimesterof pregnancies achieved following in-vitro fertilization (IVF)and embryo transfer in a group of women who delivered before(n = 8) or at term (n = 52). Those women who had a preterm deliveryhad significantly lower concentrations of PAPP-A (weeks 7–13;P = 0.0001–0.028) and SP-1 (weeks 6–8 and 10–12;P = 0.004–0.04). After correction of birth weight forsex and gestational age at delivery, preterm delivery was foundnot to be associated with growth retardation. However, comparisonof the circulating concentrations of the substances analysedin mothers who delivered babies of < 85% of the 50th centileof the normal range of birth weight for a given gestationalage and sex, with those who delivered babies of >85% revealedthat the concentrations of HCG (P = 0.012–0.04 on weeks6–9) and SP-1 (P = 0.003–0.03 on weeks 7, 9–13)were significantly lower in the former group. Weak, inconsistentassociations were found between the circulating concentrationsof HCG, SP-1 and PAPP-A and both corrected birth weight andgestational age at delivery. Thus, both the gestational ageat delivery and low birth weight may be related to impairedplacental development/function during the first trimester.     

Early and late presentation of the ovarian hyperstimulation syndrome: two distinct entities with different risk factors

This study was designed to identify clinical predictors forearly and late ovarian hyperstimulation syndrome (OHSS). A retrospectiveanalysis of all 592 in-vitro fertilization (IVF) cycles fromthe programme's inception in 1988 up to March 1993 was performed.Six patients (1.0° of cycles) had moderate or severe OHSSpresenting 3–7 days post-human chorionic gonadotrophin(HCG), and four patients (0.7° of cycles) had severe OHSSpresenting 12–17 days post-HCG. No patient with earlyOHSS went on to develop late OHSS, and no patient with lateOHSS had demonstrated early OHSS. Stepwise logistic regressionshowed that early OHSS was predicted by the number of oocytesretrieved (range 18–46) (P= 0.0001) and the oestradiolconcentration on the day HCG was given (range 12 122–24454 pmol/1) (P = 0.0003). Late OHSS was predicted by the numberof gestational sacs (range 2–3) on ultrasound 4 weeksafter embryo transfer (P = 0.0001) but not by the number ofoocytes or oestradiol. Early OHSS was an acute effect of theHCG administered prior to egg retrieval in women with high oestradioland larger numbers of follicles (range 22–51). Late OHSSwas induced by the rising serum concentration of HCG producedby the early pregnancy, and in this series of cases it was associatedonly with multiple gestation.     

Placental and ovarian hormones in anembryonic pregnancy

The circulating levels of human chorionic gonadotrophin (HCG),pregnancy-associated plasma protein-A (PAPP-A), Schwangerschaftprotein 1 (SP-1), oestradiol and progesterone were measuredin 81 pregnant patients between 4 and 11 weeks gestation, followingin-vitro fertilization and embryo transfer. The patients weredivided as follows: singleton anembryonic pregnancies, n = 22;singleton pregnancies which spontaneously aborted followingthe demonstration of fetal heart activity, n = 7; and normalsingleton pregnancies, n = 52. The levels of all substancesmeasured were significantly reduced in women with anembryoniccompared to those with singleton pregnancies which proceededto term. The serum levels of SP-1, weeks 6–8 (P < 0.01);HCG, weeks 6–8 (P < 0.05); oestradiol, weeks 5–8(P < 0.05) and progesterone, weeks 6–8 (P < 0.05),were lower in anembryonic pregnancies than in those of pregnancieswhich spontaneously aborted. These differences may be a reflectionof the fact that miscarriage, after the demonstration of fetalheart activity, represents fetal demise at a later stage inpregnancy. In anembryonic pregnancies, significant associationswere found between HCG and both oestradiol and progesteronelevels from weeks 6 and 8, suggesting that in the absence ofan embryo, HCG is the prime determinant of steroid synthesisby the corpus luteum.     

Endocrinology: Pre-ovulatory progesterone growth rate in patients treated with gonadotrophin-releasing hormone agonist and outcome of in-vitro fertilization

The present study was undertaken to assess whether the increasein serum progesterone concentration following the administrationof human chorionic gonadotrophin (HCG) may have predictive valueon the in-vitro fertilization (IVF) success rate. Progesteroneconcentration on the day of HCG administration and the increasein progesterone concentration on the following day were evaluatedin 140 consecutive patients undergoing IVF with embryo transfer.Stimulation protocol in all study patients entailed intranasaladministration of short-acting gonadotrophin-releasing hormoneagonist (GnRHa) buserelin and human menopausal gonadotrophin.A pregnancy rate of 37.2% was achieved when at least three embryoswere transferred. The only significant difference between conceptionand non-conception cycles was found in serum progesterone concentrationsafter HCG administration (P < 0.01), whereas the mean progesteroneconcentration on the day of HCG did not differ. No differencein other hormonal or cycle parameters was observed. The increasein progesterone concentration was significantly greater in thegroup of patients who achieved pregnancy than in the group whodid not (2.2 ± 0.2 versus 1.6 ± 0.1 ng/ml, respectively;P < 0.01). A critical breakpoint in serum progesterone wasarbitrarily determined at 1 ng/ml. An increase in progesteroneconcentration 1 ng/ml when three or more embryos were transferredwas associated with a positive predictive value for pregnancyof 40.4% (sensitivity of 94.7%), whereas a negative predictivevalue of 86.7% was obtained when this value was <1 ng/ml.These findings indicate that an adequate rise in serum progesteronefollowing HCG administration provides useful information aboutthe possible outcome of the treated cycle.     

FSH-induced resumption of meiosis in mouse oocytes: effect of different isoforms.

The ability of different isoforms of follicle stimulating hormone (FSH) to induce the resumption of meiosis in cultured mouse oocytes was evaluated. Oocytes were cultured in the presence of hypoxanthine to prevent spontaneous resumption of meiosis. Using serial dilutions of the isoform fractions representing less acidic isoforms (pI 6. 43-5.69), mid-acidic (pI 5.62-4.96) and acidic (pI 4.69-3.75), the concentration which caused 50% of the oocytes to resume meiosis and undergo germinal vesicle breakdown (GVBD) after a culture period of 24 h (i.e. ED(50%) GVBD) was determined. The FSH concentration of the isoform fractions was determined by radioimmunoassay, radio-receptor assay or through cAMP release in a Chinese hamster ovary-cell line expressing the human FSH-receptor. Determined by radioimmunoassay, the (ED(50%) GVBD) values were: less acidic 6.4 +/- 0.3 IU/l (mean +/- SD), mid-acidic 6.1 +/- 0.7 IU/l and acidic 12.2 +/- 0.7 IU/l. The less and mid-acidic isoforms were significant lower than the acidic (P < 0.0005). Similar relationships between the isoform fractions were obtained by the two other FSH assays. The results demonstrate that FSH isoforms with a pI of >5.0 induced resumption of meiosis significantly more efficiently than acidic isoforms. Less and mid-acidic isoforms may exert an important physiological function by inducing the resumption of meiosis in oocytes from pre-ovulatory follicles during the mid-cycle gonadotrophin surge.     

Accumulation of human chorionic gonadotrophin in the serum of patients during in-vitro fertilization treatment cycles with Pergonal

We examined the possible contribution of human chorionic gonadotrophin(HCG) in Pergonal to the serum luteinizing hormone (LH)-likebioactivity in 10 patients (median age32 years, range 28–38)with tubal infertility who were undergoing in-vitro fertilization(IVF), together with 19 controls (median age30 years, range21–43). IVF patients were treated with clomiphene (50mg twice daily) over days 2–6 and Pergonal (150 IU i.m.)daily from day 5 until at least day 10. Serum LH was measuredby fluoro-immunometric assay (I-LH) and in-vitro Leydig cellbioassay (B-LH). Serum HCG was measured by fluoro-immunometricassay. The data were analysed by paired two-tailed t-test, followinglogarithmic transformation. From days 1–5, there was anincrease in serum B-LH (mean, 95% confidence intervals givenin parentheses) from 8.3 (6.8, 10.2) IU/1 to 11.7 (9.8, 13.9)IU/1 [P= 0.004], and in serum I-LH from 4.5 (3.7, 5.4) IU/1to 5.4 (4.6, 6.3) IU/1 [P= 0.002]. From days 5–8, therewas a rise in B-LH to 16.6 (12.6, 21.9) IU/1 [P= 0.023]. Therise in I-LH to 6.3 (5.1, 7.8) IU/1 [P= 0.081] failed to reachsignificance. Furthermore, serum HCG was <<0.75 IU/1 untilafter Pergonal was administered on day 5, then rose to a plateauon day 8 at 1.2(0.8, 1.6) IU/1. Serum HCG in the controls remained<<0.75 IU/1 throughout. We conclude there is a disproportionateincrease in serum B-LH compared to I-LH from days 5–8,corresponding with a rise in serum HCG and the commencementof treatment with Pergonal. The HCG in Pergonal may be contributingto an undesirable rise in serum LH-like bioactivity, which mightreduce the success rate of IVF.     

Molecular interactions during pregnancy: Placental mRNA expression of {alpha} and {beta} human chorionic gonadotrophin in early trisomy 18 pregnancies

The placental expression of human chorionic gonadotrophin (HCG)I- and ß-subunits was investigated in eight pregnanciespresenting with trisomy 18 and in 30 normal pregnancies at 11–15weeks gestation. In the control group, the median densitometricscores of placental ß-HCG and I-HCG mRNA were 1.23and 1.74 respectively. In the trisomy 18 group the median ß-HCGmRNA was significantly lower (0.16, Z = 2.29, P<0.05) but     

The benefits of mid-luteal addition of human chorionic gonadotrophin in in-vitro fertilization using a down-regulation protocol and luteal support with progesterone

Luteal support is essential in in-vitro fertilization (IVF)when long-acting gonadotrophin-releasing hormone agonist (GnRHa)is used. Because progesterone lacks luteotrophic stimulation,it seems to be the drug of choice in cases with an increasedrisk of ovarian hyperstimulation syndrome (OHSS). The aim ofthis study was to assess the beneficial effect of the mid-lutealaddition of human choriomc gonadotrophin (HCG) in IVF, usinga down-regulation protocol and luteal support with progesterone,in a prospective randomized study. The study included 170 IVFcycles down-regulated with long-acting GnRHa which were supportedwith 50 mg/day progesterone i.m. during the luteal phase. Patientswere evaluated in the mid-luteal period. Those without clinicalsigns of OHSS, oestradiol concentrations <1000 pg/ml andprogesterone concentrations <50 mg/ml were randomly allocatedto either the addition of 2500 IU HCG (HCG+ group) or no HCG(HCG– group). End luteal phase progesterone concentrationsamong non-pregnant patients were used to assess the contributionof exogenous progesterone and to categorize pregnancies accordingto their corpus luteum function. Similar low OHSS (2.7 and 1.8%)and pregnancy (30 and 29%) rates were observed in the HCG+ andHCG– groups respectively. Of the 26 pregnancies in theHCG+ cases, there was only one case with reduced corpus luteumfunction, compared with 12 of the 25 pregnancies among HCG–patients. Cases with reduced corpus luteum function requiredcontinuous progesterone support and presented lower HCG concentrationsand a higher rate of adverse pregnancy outcome. We concludethat mid-luteal HCG addition does not affect pregnancy rate,but in fact helps to preserve corpus luteum function and avoidsthe need for further supplementation during early pregnancy.     

Endocrinology: Pituitary down-regulation prior to in-vitro fertilization and embryo transfer: a comparison between a single dose of Zoladex depot and multiple daily doses of Suprefact

In order to further evaluate the endocrinological, embryologicaland clinical efficacy of a single injection of the gonadotrophin-releasinghormone (GnRH) analogue Zoladex (goserelin), 142 women underwentpituitary down-regulation prior to in-vitro fertilization andembryo transfer: 71 with a single injection of Zoladex depot(group I) and 71 matched controls with multiple daily injectionsof Suprefact (buserelin; group II). Ovarian stimulation wasperformed with human menopausal gonadotrophin (HMG) and ovulationinduction with human chorionic gonadotrophin (HCG). HMG andhydroxyprogesterone caproate depot were given for luteal phasesupport. The mean (± SD) age (34.01 ± 4.42 versus34.81 ± 4.00 years), mean total dosage of HMG (61.25± 26.87 versus 56.17 ± 25.18 ampoules), mean dailydosage of HMG (4.74 versus 4.94 ampoules), duration of HMG stimulation(12.91 ± 3.68 versus 11.31 ± 3.46 days) and oestradiolconcentration on the day of HCG (10 082 ± 8007 versus9440 ± 7840 pmol/l) were similar in both groups but themean total number of injections (GnRH and HMG) (13.55 ±3.35 versus 55.37± 31.92) was significantly lower ingroup I. Furthermore, the proportion of women down-regulatedby 2 weeks and pregnancy rate per embryo transfer were significantlyhigher in the Zoladex group, while miscarriage rates were similar.We conclude that a single dose of Zoladex is quicker, more convenientand should be investigated as an equally effective alternativeto mutiple doses of Suprefact for pituitary down-regulationprior to assisted conception. Further studies are required totest the teratogenicity and effectiveness of Zoladex.     

Pregnancy: Endometrial ultrasonography as a predictor of pregnancy in an in-vitro fertilization programme

The endometrial pattern and thickness were analysed by ultrasonographyin 139 cycles stimulated for in-vitro fertilization (IVF) onthe day of administration of human chorionic gonadotrophin (HCG).A semi-programmed schedule based on the pill + clomiphene citrate+ human menopausal gonadotrophin (HMG) was used in all cycles.On the day of HCG administration, endometrial pattern and thicknesswere assessed with an Ultramark 4 (ATL) ultrasound equippedwith a 5 MHz vaginal probe. Endometrial pattern I (a ‘tripleline’multilayer) was observed in a total of 105 cycles (76%), andpattern II (fully homogeneous and hyperechogenic in relationto myometrial tissue) in 34 (24%). The incidence of clinicalpregnancy did not differ (P = 0.52) between the groups withendometrial patterns I (23.8%) and II (29.4%). Endometrial thicknesson the day of HCG administration in the group with pattern I(8.4 ± 1.9 mm) was similar (P = 0.96) to that observedin the group with pattern II (8.4 ± 2.0 mm). In addition,the endometrial thickness of the patients who became pregnant(8.0 ± 1.7 mm) did not differ (P = 0.15) from that ofwomen who did not achieve pregnancy (8.6 ± 2.0 mm). Theconclusion from the present data is that ultrasonographic analysisof endometrial thickness and refringency on the day of HCG administrationhad no predictive value for conception in IVF cycles.     

Endocrinology: A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility

The use of gonadotrophin-releasing hormone agonist (GnRHa) incombination with human menopausal gonadotrophin (HMG) for ovulationinduction has been advocated for the treatment, particularlyby in-vitro fertilization (IVF) of various types of infertility.The present study was designed to compare the clinical efficacyof HMG alone with a short protocol of GnRHa/HMG for treatmentof unexplained infertility. A total of 91 couples with unexplainedinfertility were randomly assigned to one of two treatments;either HMG with intra-uterine insemination (IUI) (45 patients,62 cycles) or GnRHa/HMG with IUI (46 patients, 69 cycles) treatments.Progesterone concentrations on the day of human chorionic gonadotrophin(HCG) administration were significantly higher in HMG (1.5 ±0.9 ng/ml) versus GnRHa/HMG (0.8 ± 0.6 ng/ml; P <0.05)cycles. Furthermore, GnRHa suppressed the occurrences ofpremature luteinization (GnRHa/HMG 5.8% and HMG 24.2% respectively).However, there were no significant differences in HMG dose requirements,plasma oestradiol concentrations or follicular development onthe day of HCG administration between the two groups. Nor wereany significant differences found in the pregnancy rates betweenthe two treatment protocols (GnRHa/HMG 13.0% and HMG 11.3% respectively).Our results suggest no beneficial effect of GnRHa/HMG comparedto HMG alone for the treatment of unexplained infertility, basedon pregnancy rates.     

Endocrinology: The empty follicle syndrome: a pharmaceutical industry syndrome

The purpose of this study is to provide evidence that emptyfollicle syndrome (EFS) is a result of an abnormality in thein-vivo biological activity of some batches of commerciallyavailable human chorionic gonadotrophin (HCG). This is a comparativestudy between six consecutive in-vitro fertilization (IVF) caseswith EFS (study group) and 10 IVF pregnancy cycles (controlgroup). Both groups received the same ovarian stimulation protocolconsisting of leuprolide acetate and human menopausal gonadotrophin(HMG). An i.m. injection of 10 000 IU of HCG was administeredonce follicles had reached 18–20 mm and oestradiol/follicle16 mm was at least 900 pmol/l. Transvaginal aspiration was performed36 h later. Plasma HCG prior to and 12 h after i.m. injectionas well as the follicular fluid (FF) concentrations of oestradiol,progesterone, luteinizing hormone (LH) and HCG were determinedin the study group and controls. The in-vitro biological activityof the batch of HCG used by the EFS cases and the control groupwas determined using a Leydig cell preparation from adult rats.Furthermore, the plasma clearance rate after i.v. injectionof 5000 IU of HCG, from the same batches, was studied in threemale volunteers. In the IVF cycles, no HCG was detected in plasmaprior to the injection of commercial HCG. After 12 h, no HCGwas detected in the study group compared to a mean of 207.5IU/l (110–360) in controls. Mean FF concentration of LH,HCG, progesterone and oestradiol was 0.9 IU/1, 0 IU/l, 3.1 nmol/mland 4.4 nmol/ml in EFS compared to 1.0, 98.3, 32.0 and 3.7 inpregnancy cycles. The in-vitro biological activity in both HCGbatches was not significantly different; however, immunoreactiveHCG used in EFS cases was undetectable in plasma of male volunteersas soon as 10 min after i.v injection of 5000 IU of HCG. Theendocrine abnormalities found in follicular fluids of EFS arenot a consequence of an ovarian problem but the result of alack of exposure to biologically active HCG. The rapid clearanceof the drug after i.v. injection and the high affinity of desialylatedHCG to liver cells suggest this to be a possible explanationfor this infrequent but unfortunate event.     

Endocrinology: The effects of gonadotrophin-releasing hormone agonist on follicular development in patients with polycystic ovary syndrome in an in-vitro fertilization and embryo transfer programme

The aim of the study was to evaluate ovarian response to gonadotrophinstimulation, with and without premedication with gonadotrophin-releasinghormone (GnRH) agonist, in patients with polycystic ovary syndrome.In all, 40 women included in the in-vitro fertilization/embryotransfer programme were divided into two groups. In the firstgroup, buserelin, 500 µg/day s.c., was given until pituitarydesensitization was achieved. Ovarian stimulation was performedby the combination of GnRH agonist and human menopausal gonadotrophin(HMG). The second group was treated using a conventional HMGand human chorionic gonadotrophin(HCG) protocol. Desensitizationwas achieved in 15.2 ± 6.3 days (mean ± SD) andthe luteinizing hormone:follicle stimulating hormone ratio decreasedfrom 2.84± 1.54 to 0.60 ±0.35. Comparing the durationof stimulation, the number and size of all observed and aspiratedfollicles, oocytes recovered and fertilized and the number ofembryos replaced, no statistically significant differences werefound between the groups. The average oestradiol concentrationon the day of HCG administration was lower in the group treatedwith premedication (P< 0.05). These data suggest that shortpre-treatment with GnRH agonist can temporarily correct endocrineabnormalities of polycystic ovary syndrome but do not changethe ovarian response to gonadotrophin stimulation and multiplefollicular development.     

Choriocarcinoma-like human chorionic gonadotrophin (HCG) and HCG bioactivity during the first trimester of pregnancy

The objective of this study was to evaluate the distribution of choriocarcinoma-like human chorionic gonadotrophin (HCG) isoforms during first trimester pregnancy and their relationship with in-vitro HCG bioactivity. This was done by means of a retrospective analysis of patients' sera with first trimester normal intrauterine and abnormal (ectopic) pregnancies. Serum samples were obtained from 38 women with an amenorrhoea of <10 weeks. From these, 19 had a normal intrauterine pregnancy (IUP) and 19 an ectopic pregnancy (EP). Total immunoreactive HCG (HCGi), free beta-HCGi and oestradiol were measured by enzyme immunoassays and bioactive HCG by the mouse Leydig cell bioassay. The alterations in HCG isoform content were measured by the combination of two immunometric assays, B152 for choriocarcinoma-like HCG and B109 for intact HCG detection and expressed as the B152/B109 ratio. Choriocarcinoma-like HCG isoforms ratio measured by B152 and B109 assays was significantly higher in the low subgroups of free beta-HCGi and gestational age (P = 0.0111 and 0.0036 respectively). Whereas bioactive to immunoreactive HCG ratios (b/i ratio) were significantly higher when free beta-HCGi concentrations were low (P = 0.0010), no correlation was found between the variation of bioactivity (b/i ratio) and the proportion of choriocarcinoma-like HCG isoforms (B159/B108). It is concluded that in first trimester pregnancies (i) the modulation of HCG in-vitro bioactivity is not related to the variation of choriocarcinoma-like HCG isoforms secretion and (ii) the amount of choriocarcinoma-like HCG isoforms secreted by the early trophoblast is predominant and may be the result of an early developmental regulation of glycosylation enzyme.     

Human prolactin release induced by follicle stimulating hormone, luteinizing hormone and human chorionic gonadotrophin

Plasma prolactin levels rise in stimulated cycles. To clarifythe effects of gonadotrophin on the lactotrophs, three studieswere performed. First, plasma concentrations of prolactin duringclomiphene citrate (CC)-human menopausal gonadotrophin (HMG)-humanchononic gonadotrophin (HCG) treatment of women enrolled forin-vitro fertilization (IYF) were compared with those duringHMG-HCG administration while under pituitary suppression witha gonadotrophin releasing hormone (GnRH) analogue (buserelin).Women suppressed with buserelin had higher basal levels of PRLin plasma (14.4 ± 4.3 nglml versus 6.9 ± 1.4 ng/ml,P<0.001). Only buserelin-suppressed women showed a significantrise in plasma prolactin before HCG administration, while bothpatient groups had marked prolactin peaks after HCG injection.This peak was higher in the buserelin group (71.9 ± 50.7ng/ml versus 52.6 ± 29.7 ng/ml). The second study showedthat plasma levels of prolactin of 6 post- menopausal womenwere significantly increased 48 h after an injection of 5000IU HCG, i.m. (24.9 ± 17.4 ng/ml versus 12.4 ±6.2 ng/ml P<0.05). Third, plasma prolactin was studied in5 women over 30 days after surgical castration. An upward trendwas observed similar to that of endogenous gonadotrophin, withthe change in prolactin values closely correlating with thechange in concentrations of follicule stimulating hormone (P<0.005).All these findings suggest that human gonadotrophins stimulatelactotrophs.     

Pregnancy: Premature luteinization as detected by elevated serum progesterone is associated with a higher pregnancy rate in donor oocyte in-vitro fertilization

Premature luteinization has been reported to be associated withdecreased pregnancy rates in patients undergoing in-vitro fertilization.However, the detrimental effect created by a pre-aspirationrise in progesterone is difficult to assess since ovarian stimulationaffects both oocyte quality and endometrial receptivity. Therefore,the relationship between premature luteinization and pregnancyrates remains uncertain. To achieve improved control for confoundingvariables, we studied premature luteinization in ovum donorsof proven fertility. A total of 114 consecutive ovum donationcycles using pituitary suppression with a gonadotrophin-releasinghormone agonist followed by gonadotrophin stimulation were examined.Serum progesterone concentration on the day of administrationof human chorionic gonadotrophin (HCG) was > 1.2 ng/ml in29% of patients. Patients were divided into two groups basedon this value. There was a significant increase in clinicalpregnancy rates per embryo transfer in the group with higherprogesterone concentrations (53 versus 25%, P = 0.012), as wellas significantly more oocytes obtained at aspiration (19.6 ±10.4 versus 13.3 ± 5.4, P < 0.001), and significantlyhigher peak serum oestradiol values (3903 ± 1787 versus2453 ± 1232 pg/ml, P < 0.001). There were no significantdifferences between groups due to age, degree of stimulationor the number of embryos transferred. We conclude that prematureluteinization as based on elevated serum progesterone concentrationis a common occurrence in oocyte donors, reflects healthy folliculardevelopment, and is associated with increased pregnancy rates.     

Studies on the relative in-vitro biological potency of the naturally-occurring isoforms of intrapituitary follicle stimulating hormone

In the present study, we analysed and compared the relativein-vitro biological activity of the various intrapituitary humanfollicle stimulating hormone (FSH) isoforms employing two differentbioassay systems. FSH was fractionated by chromatofocusing (pHrange 7.10 to <3.80) and the several isoforms isolated werequantified at multiple dose levels by three highly specificimmunoassay systems: radioimmunoassay (RIA), enzyme-immunoassay(EIA) and immunoradiometric assay (IRMA), as well as by twoin-vitro bioassays, one that measures the amount of oestrogenproduced by rat granulosa cells in culture and the other thatdetermines the amount of cAMP produced by a human fetal cellline (293) expressing the recombinant human FSH receptor. Therelative in-vitro biological activity of each FSH isoform, expressedas the bioassay/ immunoassay (B/I) activity ratio (B/RIA, B/EIAand B/IRMA ratios) varied with its elution pH value. Regardlessof the immunoassay or bioassay method employed, less acidicFSH isoforms exhibited higher B/l ratios than their more acidiccounterparts (B/RIA, B/EIA and B/IRMA ratios for isoforms withelution pH values >4.5 = 1.05 ± 0.13, 0.99 ±0.10 and 1.15 ± 0.08 (rat oestrogen bioassay), and 2.75± 0.34, 2.20 ± 0.25 and 2.96 ± 0.35 (humancAMP production bioassay) respectively. Ratios for isoformswith pH values <4.5 = 0.71 ± 0.06, 0.47 ± 0.05and 0.63 ± 0.06 (rat oestrogen assay), and 1.80 ±0.26, 1.10 ± 0.09 and 1.44 ± 0.13 (cAMP assay)respectively (P<0.05 for isoforms with pH <4.5 comparedwith those isoforms with pH >4.5)]. Furthermore, statisticallysignificant direct relationships between the B/RIA, B/EIA andB/IRMA ratios and the elution pH value of each isoform was identifiedby regression analysis [rat assay: r = 0.844, 0.800 and 0.780(P<0.01); human assay: r = 0.730, 0.845 and 0.821 (P<0.01),for their corresponding B/RIA, B/EIA and B/IRMA ratios respectively].The finding of significant differences in relative in-vitrobiological potency among the various intrapituitary FSH isoformsstrongly suggests that the shifts towards the production andsecretion of more basic or acidic FSH molecules occurring incertain specific physiological conditions (e.g. puberty andmenstrual cycle), may represent an important mechanism throughwhich the anterior pituitary regulates gonadal function. follicle stimulating hormone/FSH bioactivity/FSH glycoforms/granulosa cells/recombinant FSH receptor     

HCG concentration and receptor gene expression in placental tissue from trisomy 18 and 21

Trisomy 21 is associated with high maternal serum concentrationsof intact human chorionic gonadotrophin (HCG) and free ß-HCGwhereas these concentrations are markedly decreased in trisomy18. In this study, we investigated the effect of trisomy 21and 18 on endogenous HCG concentrations and luteinizing hormone(LH)/HCG receptor expression in placental villous tissue ineight trisomy 21, six trisomy 18 and 42 chromosomally normalsamples, collected at 12–16 weeks gestation. The tissueconcentrations of intact HCG, free -HCG and free ß-HCGsubunits were measured using solid-phase two-site immunoradiometricassay. LH/HCG receptor expression was evaluated with immunohistochemistryand in-situ hybridization. Villous tissue in trisomy 21 containedhigher ß-HCG concentrations than the controls (P <0.05). In trisomy 18 cases, the ß-HCG concentration waslower than in the control group (P < 0.01). Both immunocytochemistryand in-situ hybridization demonstrated a more intense stainingof the trophoblast in cases of trisomy 21 and 18, compared withcontrols with the strongest signal in cases of trisomy 18 (P< 0.01). We concluded that in trisomy 21 the high tissueHCG concentration and expression of LH/HCG receptor in the trophoblastmay reflect the relative immaturity of the trophoblastic tissuewhereas in trisomy 18, the very low concentration of endogenousHCG, associated with an over-expression of LH/HCG receptor inthe trophoblast, is probably secondary to the poor differentiationof the cytotrophoblast. HCG/placenta/pregnancy/receptors/trisomy Notes ⁴ To whom correspondence should be addressed at: Academic Departmentof Obstetrics and Gynaecology, University College London MedicalSchool, 86–96 Chenies Mews, London WC1E 6HX, UK