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.     

Association of early {beta}-human chorionic gonadotrophin values with pregnancy wastage and multiple implantation in a donor oocyte programme

An early marker predictive of a viable pregnancy would easethe anxiety associated with positive pregnancy tests after theuse of donor oocytes. We examined the predictive value of anearly serum quantitative human chorionic gonadotrophin (Q-HCG)concentration on pregnancy outcome following oocyte donation.Embryo transfers after oocyte donation resulting in a positiveserum -HCG were examined beginning 9 days after embryo transferfrom those samples assayed in our laboratory (n = 77). Q-HCGconcentrations were measured in our laboratory by an immunoradiometricassay utilizing the first International Reference Preparation.Implantations were defined as the number of gestational sacsvisualized by transvaginal ultrasound 21 days after embryo transfer.Biochemical pregnancies were those with transient elevationsin -HCG concentration but without implantation sites. Spontaneousabortions were characterized by an implantation site with theeventual arrest of development. Ongoing/delivered pregnanciesdeveloped appropriately and proceeded beyond the first trimester.Day 9 Q-HCG concentrations did not differentiate between biochemicalpregnancies/spontaneous abortions and ongoing/delivered pregnancies,although mean ± SD concentrations for biochemical pregnancieswere significantly lower than those for the other groups (P< 0.0001): biochemical pregnancies, n = 18, 5.8 ±8.9 mlU/ml, range 0–35; spontaneous abortions, n = 2,46.0 ± 10.0 mlU/ml, range 39–53; ongoing/deliveredpregnancies, n = 57, 41.5 ± 35.4 mlU/ml, range 0–214.In addition, day 9 Q-HCG concentrations did not differentiatebetween multiple implantations, although the implantation offour sacs had a significantly higher mean Q-HCG concentrationcompared with the implantation of fewer sacs (P > 0.0001):one sac, n = 22, 32.2 ± 21.5 mlU/ml, range 3–78;two sacs, n = 25, 35.8 ± 21.3, range 0–81; threesacs, n = 7, 47.1 ± 37.1 mlU/ml, range 22–126;four sacs, n = 4, 122.3 ± 62.4 mlU/ml, range 76–214.The positive predictive value of a Q-HCG >10 mlU/ml was 0.91(sensitivity 91%, specificity 75%). These initial data suggestthat early day 9 serum Q-HCG determinations do not accuratelyidentify viable pregnancies or multiple implantations. Evenan early negative pregnancy test should be repeated becauseit can be associated with a normal pregnancy.     

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.     

Endocrinology: Luteal function following ovulation induction in polycystic ovary syndrome patients using exogenous gonadotrophins in combination with a gonadotrophin-releasing hormone agonist

The luteal phase was studied in 12 polycystic ovary syndrome(PCOS) patients following ovulation induction using exogenousgonadotrophins combined with a gonadotrophin-releasing hormoneagonist (GnRH-a). Human menopausal gonadotrophin (HMG) was precededby 3 weeks of treatment with GnRH-a (buserelin; 1200 µg/dayintra-nasally) and administered in a step-down dose regimenstarting with 225 IU/day i.m. GnRH-a was withheld the day beforeadministration of human chorionic gonadotrophin (HCG; 10 000IU i.m.). Blood sampling and ultrasound monitoring was performedevery 2–3 days until menses. The luteal phase was significantlyshorter in PCOS patients as compared to eight regularly cyclingcontrols: 8.8 (3.3–11.4) days [median(range)] versus 12.8(8.9–15.9) days (P = 0.01). Median peak values for progesteronedid not show significant differences comparing both groups:52.3 (17.1–510.3) nmol/l versus 43.0 (31.2–71.1)nmol/l, respectively (P = 0.8). The interval between the dayof the progesterone peak and return to baseline was significantlyshorter in the PCOS patients than in controls: 2.5 (0.3–4.9)days versus 4.2 (3.9–10.5) days (P < 0.005). Luteinizinghormone (LH) concentrations during the luteal phase as reflectedby area under the curve were significantly lower in PCOS ascompared to controls: 4.4 (1.6–21.0) IU/l x days and 49.0(27.8–79.6) IU/l x days, respectively (P < 0.001).In conclusion, patients with PCOS may suffer from insufficientluteal phases after ovulation induction using HMG/HCG in combinationwith a GnRH-a. The corpus luteum apparently lacks the supportof endogenous LH and may be stimulated only by the pre-ovulatoryinjection of HCG. Potential involvement of adjuvant GnRH-a medicationor HCG itself in luteal suppression of endogenous gonadotrophinsecretion, and the importance of luteal function for pregnancyrates following treatment, warrant further studies.     

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     

Infertility: Predicting and optimizing success in an intra-uterine insemination programme

We analysed 381 consecutive cycles of homologous intra-uterineinsemination (IUI) in 215 infertile couples, resulting in 48pregnancies (12.6%/cycle, 22.3/patient). Cycle fecundity rangedfrom 0.11 to 0.14 in women aged 25–39 years, falling to0.04 beyond age 40 years. Of the 48 pregnancies, 43 occurredin the first three treatment cycles, in which fecundity was0.14, 0.16 and 0.10 respectively. Beyond three cycles, fecunditywas 0.07 (P = 0.05 versus first two cycles). The occurrenceof pregnancy varied with diagnosis (P = 0.04). Fecundity wassignificantly greater for women with ovulatory dysfunction (0.30)than for endometriosis, male factor, tubal factor, idiopathicinfertility or multifactorial (0.08–0.14). Ovulation inductionusing menopausal gonadotrophins offered significant advantageover natural cycles or cycles using clomiphene citrate withoutgonadotrophins (0.15 versus 0.03, P = 0.01). Cycles in whichpre-ovulatory surges were either induced or supported with humanchorionic gonadotrophin (HCG) were superior to spontaneous luteinizinghormone surges (0.13 versus 0.03, P = 0.05). Recruitment ofat least two mature (>1.6 cm) follicles was critical. Onlyone pregnancy occurred in 64 cycles characterized by one maturefollicle, compared with a pregnancy rate of 0.15 in cycles characterizedby two or more mature follicles (P = 0.006). IUI is not beneficialto women >40 years old, and has the best chance of successwithin three cycles. Multiple follicle recruitment using gonadotrophin-basedstimulation protocols and mid-cycle HCG are necessary to achievean acceptable pregnancy rate.     

Obstetric outcome after prenatal diagnosis in pregnancies obtained after intracytoplasmic sperm injection

In this study we compared the pregnancy outcome of 576 pregnanciesafter prenatal diagnosis with that of 540 pregnancies withoutprenatal diagnosis in our micro-injection programme. Amniocentesiswas suggested for singleton pregnancies (n = 465) and chorionicvillus sampling (CVS) was proposed for twin pregnancies (n =111 pregnancies, 222 fetuses). A total of 365 patients withsingleton pregnancies and 175 patients with twin pregnancieswho did not undergo prenatal diagnosis were selected as controls.Compared with the controls, the odds ratios in the amniocentesisgroup for preterm delivery, low birthweight, very low birthweightand fetal loss were 0.97 [95% confidence interval (CI): 0.60–1.57],1.27 (95% CI: 0.78–2.06), 1.57 (95% CI: 0.53–4.66)and 0.86 (95% CI: 0.32–2.37) respectively. Compared withthe controls, the odds ratios in the CVS group for preterm delivery,low birthweight, very low birthweight and fetal loss were 0.89(95% CI: 0.61–1.30), 1.03 (95% CI: 0.74–1.45), 0.79(95% CI: 0.41–1.53) and 0.47 (95% CI: 0.17–1.30)respectively. We concluded that, in this series of intracytoplasmicsperm injection (ICSI) pregnancies, prenatal testing did notincrease the preterm-delivery, the low-birthweight, or the verylow-birthweight rates as compared with those of the controls.In the prenatal diagnosis group, the fetal loss rate was comparableto that of the control group. Larger prospective controlledstudies are needed in order to inform patients reliably aboutthe risks and the advantages of prenatal testing in ICSI pregnancies.     

High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies

Antiphospholipid antibodies (APA), lupus anticoagulant (LA)and/or anticardiolipin antibodies (ACA), are associated withthrombosis and recurrent miscarriage. We studied the outcomeof 20 pregnancies in women (median age 32 years; range 23–41)with APA (14 LA positive; three immunoglobulin (Ig) G ACA positive;two IgM ACA positive and one LA and IgG ACA positive) and historyof recurrent miscarriage (median 4; range 3–11) who declinedpharmacological treatment in their next pregnancy. Comparisonwas made with a cohort of 100 consecutive women (median age33 years; range 23–44) with recurrent miscarriage (median4; range 3–10), in whom no underlying cause to accountfor their pregnancy losses was found. Of the 20 women with APA,18 (90%) miscarried compared to 34 of the 100 women (34%) withnormal investigations (P < 0.001). The majority (94%) ofmiscarriages in women with APA occurred in the first trimester.Fetal heart activity was seen prior to fetal death in 86% ofwomen with APA compared to 43% of women with normal investigations(P < 0.01). The first trimester loss of embryonic pregnanciesis the most common type of miscarriage in women with APA. Thismay be a result of defective implantation and subsequent placentation.     

Decreased maternal circulating hepatocyte growth factor (HGF) concentrations in pregnancies with small for gestational age infants

Our purpose was to evaluate whether maternal and fetal hepatocytegrowth factor (HGF) concentrations in pregnancies with smallfor gestational age (SGA) infants are different from those inpregnancies with appropriate for gestational age (AGA) infants.Maternal and fetal circulating HGF concentrations were comparedbetween 55 pregnancies with AGA infants and 16 pregnancies withSGA infants at birth. HGF concentrations were measured frommaternal and cord venous blood samples using an enzyme-linkedimmunosorbent assay. Umbilical artery blood pH and oxidativepressure (PO₂) were also measured. Maternal circulating HGFconcentrations (0.60 ± 0.35 ng/ml) in pregnancies withSGA infants were significantly lower than those (0.91 ±0.44 ng/ml) in pregnancies with AGA infants (P = 0.012). Therewere no significant differences in fetal circulating HGF concentrationsbetween both groups. No significant differences in umbilicalartery blood pH and PO₂ were found between both groups. Theseresults suggest that the maternal serum circulating HGF concentrationhas a significant role in fetal growth during pregnancy.     

Endocrinology: Randomized trial of misoprostol and cervagem in combination with a reduced dose of mifepristone for induction of abortion

Mifepristone (600 mg) in combination with a prostaglandin hasbeen demonstrated to be a safe, acceptable alternative to vacuumaspiration for induction of abortion in the first 9 weeks ofpregnancy. However, the efficacy and side-effects of differentprostaglandins used in combination with mifepristone have notbeen assessed in a randomized trial. In this study, 800 womenseeking an abortion at gestational age 63 days amenorrhoea wererandomized to receive either 0.5 mg gemeprost by vaginal pessary(group I) or 600 µg misoprostol (group II) by mouth –48h after taking 200 mg mifepristone by mouth. The side-effectsand number of complete abortions were used as measures of efficacy.There was no significant difference in the rate of completeabortion between group I [96.7%; 95% confidence interval (CI)94.9–98.5%, n = 391] and group II (94.6%; 95% CI 92.3–96.9,n = 386). It was not possible to assess the outcome with certaintyin the remaining 23 women. However, there were significantlymore ongoing pregnancies in the women who received misoprostolthan in those who received gemeprost (nine versus one, P <0.01) and in eight of these 10 women the gestation was >49days. Fewer women in group II required analgesia than in groupI (48 versus 60%, P < 0.001) although the number requestingopiate was similar in each group (6.9 versus 5.2%, P > 0.4).The incidence of nausea and vomiting after misoprostol (47.8and 21.9% respectively) was higher (P < 0.001) than aftergemeprost (33.9 and 12% respectively). The incidence of infectionand heavy bleeding was low in both groups (<2%) and onlyone woman required blood transfusion. We conclude that the recommendeddose of mifepristone and gemeprost can be reduced without impairingclinical efficacy in pregnancies up to 63 days amenorrhoea.Misoprostol is a safe alternative prostaglandin but has a higherincidence of ongoing pregnancies especially at gestation after49 days amenorrhoea.     

Relationship of biochemical pregnancy to pre-ovulatory endometrial thickness and pattern in patients undergoing ovulation induction

In order to assess the relationship between pre-ovulatory endometrialthickness and pattern and biochemical pregnancy, the pregnancyoutcome was retrospectively analysed in 81 patients undergoingovulation induction evaluated by vaginal ultrasound on the dayof human chorionic gonadotrophin (HCG) administration or luteinizinghormone (LH) surge. Biochemical pregnancies occurred in 7/32(21.9%) pregnancies when endometrial thickness was <9 mm,compared to 0/49 when endometrial thickness was 9 mm on theday of HCG administration or LH surge (P < 0.0025). Clinicalabortions occurred in 5/32 (15.6%) pregnancies when endometrialthickness was 6–8 mm, compared to 6/49 (12.2%) when endometrialthickness was 6–8 mm (NS). Endometrial thickness was relatedto the cycle day of HCG or LH surge (r = 0.37, P < 0.001)but was unrelated to oestradiol level on the day of HCG administrationor LH surge (r = 0.12). Biochemical pregnancies were relatedto endometrial pattern (r = – 0.22, P = 0.02) but wereunrelated to maternal age or previous abortions. Clinical abortionswere related to age (r = 0.26, P = 0.01) and to previous abortion(r = 0.25, P = 0.013) but were unrelated to endometrial pattern.Neither biochemical pregnancy nor clinical abortion was relatedto oestradiol or LH levels on the day of HCG administrationor LH surge. These findings suggest that the majority of biochemicalpregnancies do not result from karyotypically abnormal embryos,as do clinical abortions.     

Pregnancy: Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older

We analysed the results of oocyte donation to women of advancedreproductive age (45 years old) and followed their pregnanciesthrough to delivery in order to assess obstetrical outcomes.Patients (n = 162) aged 45–59 years (mean ± SD;47.3 ± 3.4 years) underwent 218 consecutive attemptsto achieve pregnancy. Oocytes (16.2 ± 7.2 per retrieval)were provided by donors 35 years old. Cleaving embryos (8.2± 4.8 zygotes/couple) were transferred trans-cervically(4.5 ± 1.1 per embryo transfer) to recipients prescribedoral micronized oestradiol and intramuscular progesterone. Followingoocyte aspiration there were six instances of non-fertilization(2.8%) and 212 embryo transfers. A total of 103 pregnancieswas established for an overall pregnancy rate (PR) of 48.6%,which included 17 preclinical pregnancies, 12 spontaneous abortions,and 74 delivered pregnancies (clinical PR 40.6%; delivered PR34.9%). Multiple gestations were frequent (n = 29; 39.2% ofpregnancies) and included 20 twins, seven triplets, and twoquadruplets. Two of the triplet and both of the quadruplet pregnanciesunderwent selective reduction to twins. Antenatal complicationsoccurred in 28 women (37.8% of deliveries) and included pretermlabour (n = 9), gestational hypertension (n = 8), gestationaldiabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia(n = 2), HELLP syndrome (n = 2), and fetal growth retardation(n = 2). 48 (64.8%) deliveries were by Caesa-rean section. Thegestational age at delivery for singletons was 383 ±1.3 weeks (range 35–41 weeks), with birth weight 3218± 513 g (range 1870–4775 g); twins 35.9 ±2.0 weeks (range 32–39 weeks), birth weight 2558 ±497 g (range 1700-3450 g); and triplets 33.5 ± 0.7 weeks(range 32-34 weeks), birth weight 1775 ± 190 g (range1550-2100 g). Neonatal complications (4.6% of babies born) includedgrowth retardation (n = 2), trisomy 21 (n = 1), ventricularseptal defect (n = 1), and small bowel obstruction (n = 1).There were no maternal or neonatal deaths. We conclude thatoocyte donation to women of advanced reproductive age is highlysuccessful in establishing pregnancy. However, despite carefulantenatal screening, obstetrical complications are common, oftensecondary to multiple gestation.     

Atrial natriuretic peptide, oestradiol and progesterone in women undergoing spontaneous and gonadotrophin-stimulated ovulatory cycles

The objective of this study was to examine the relationshipbetween the concentrations of oestradiol and progesterone onthe one hand and atrial natriuretic peptide (ANP) concentrationson the other, during the follicular and luteal phases of spontaneousand gonadotrophin-stimulated ovulatory menstrual cycles. A totalof 27 ovulatory women undergoing either a spontaneous (n = 9)or a gonadotrophin-stimulated (n = 18) cycle were selected forinclusion in this study. In comparison with spontaneous cycles,gonadotrophin-stimulated cycles had increased peak follicularoestradiol (mean ± SE; 937 ± 150 versus 195 ±18 pg/ml; P < 0.05) and midluteal progesterone (mean ± SE; 44.0 ± 7.4 versus 14.1 ± 2.4 ng/ml; P <0.05) concentrations. There were no differences in the circulatingANP concentrations between the follicular and luteal phasesof the menstrual cycle. Despite the increased oestradiol andprogesterone concentrations following gonadotrophin stimulation,no difference in ANP concentrations was seen between stimulatedand spontaneous cycles. There was no correlation between circulatingconcentrations of oestradiol, progesterone (at physiologicaland supraphysiological concentrations) and ANP throughout themenstrual cycle.     

Implantation: Variations in concentrations of the major endometrial secretory proteins (placental protein 14 and insulin-like growth factor binding protein-1) in assisted conception regimes

We have previously shown that placental protein 14 (PP14) concentrationswere depressed in two pregnancies that followed down-regulationof the anterior pituitary and exogenous hormone support priorto a frozen—thawed embryo transfer. We now report on amore comprehensive series of pregnancies following this formof treatment, in-vitro fertilization (IVF) and natural cyclefrozen—thawed embryo transfer. Serum specimens were analysedfor PP14 and insulin-like growth factor binding protein-1 12days after embryo transfer and at 7 weeks gestation. At 12 daysafter embryo transfer, the mean serum PP14 concentrations inthe IVF and natural cycle were significantly higher in thosewho conceived than those who did not (82 versus 23 and 107 versus39 µg/l respectively, P < 0.001). Although the meanPP14 concentration in the hormone-supported pregnant patientswas higher than in the non-pregnant patients, this had not reachedstatistical significance 12 days after embryo transfer (49 versus31 µg/1). By 7 weeks gestation the PP14 concentrationsin the hormone-supported pregnant patients were significantlyhigher than in the non-pregnant patients (152 versus 31 µg/1,P < 0.001). However, the PP14 concentrations for hormone-supportedpregnant patients were significantly lower (P < 0.001) thanthose for pregnant IVF or natural cycle patients at 7 weeksgestation (152, 777 and 660 µg/l respectively). The PP14concentrations in the pregnant patients, although lower thanthose in IVF and natural cycle pregnancies, were higher thanthose previously reported in ovarian failure and Turner's syndromeovum donation cycles. Patients treated by down-regulation andexogenous hormones had significantly higher serum IGFBP-1 concentrationsthan IVF and natural cycle patients at 7 weeks gestation (P0.01); mean concentrations 107, 58 and 43 µg/l respectively).Elevated IGFBP-1 concentrations may influence the rise in PP14concentrations in these patients.     

Vascular anatomy of monochorionic placenta in relation to discordant growth and amniotic fluid volume

The objective of this study was to determine the chorionic platevascular anatomy of the monochorionic (MC) placenta in relationto the discordance in fetal growth with or without disparityin amniotic fluid volume. In 58 MC placentae, anastomoses weredelineated by dye-contrast injection under optimal physiologicalconditions. Thirty-two pregnancies were complicated by twin-twintransfusion syndrome (TTTS) (n = 32), of which 16 placentaewere from severe disease. Ten pregnancies with fetal growthdiscordance of >20% and with a normal amniotic fluid index(AFI) were also studied. Sixteen uncomplicated MC pregnancieswere used as controls. Severe TTTS placentae (median, m 1; range,r 0 to 2) had significantly fewer anastomoses than those frommild disease (m 2; r 1 to 4; P < 0.01), discordant growth(m 3; r 2 to 6; P < 0.001) and controls (m 5; r 2 to 8; P< 0.001). Placentae from severe TTTS had a single unidirectionaldeep arteriovenous anastomosis, while milder cases, in addition,had a 1 mm bidirectional superficial arterioarterial (n = 9)or venovenous (n = 6) -type shunts. Multiple arteriovenous anastomoseswith a paucity of superficial anastomoses were detected in discordantgrowth placenta. In contrast, control placentae had multipleshunts which were symmetrical in number, type and size bothoverall and per placenta. The subchorionic distance in severeTTTS and discordant growth placenta were comparable (m 3.5 cm;r 1.6 to 5.8 cm versus m 3.6 cm; r 2.5 to 5.7 cm), but weregreater than the mild disease (m 2.5 cm; r 1.2 to 3.8 cm; P< 0.01) and control groups (m 1 cm; r 0.5 to 2.4 cm; P <0.001). The perinatal mortality in severe TTTS (57%) was higherthan that in the mild TTTS (17%) and growth discordant groups(15%). The paucity of superficial anastomoses with presenceof solitary or multiple arteriovenous anastomoses is likelyto be associated with severe TTTS and fetal growth discordanceof >20% respectively. In contrast, in mild TTTS additionalsuperficial arterioarterial or venovenous channels are presentalong with single deep arteriovenous anastomoses.     

Epidermal growth factor receptors in human corpora lutea during the menstrual cycle and pregnancy

We have demonstrated the presence of epidermal growth factor(EGF) and its receptors in human non-gestational corpora lutea.To determine further the characteristics of EGF receptor binding,we examined 30 human corpora lutea throughout the luteal phaseand during pregnancy. Scatchard plots of EGF binding in 29 ofthe 30 corpora lutea were curvilinear, suggesting negative co-operativity.The mean ± SE of the association constant K_a was (0.9± 0.2) x 10⁹ 1/mol, the dissociation constant K_d was(2.2 ± 0.3) x10^–9 mol/1 and the number of bindingsites (Rt) was (15.8 ± 2.1) x10^–19 mol/µgprotein for non-gestational corpora lutea. The K_d increasedsignificantly in late pregnancies compared to early pregnancies(P = < 0.005), while Rt was significantly higher in termpregnancies than in either early pregnancy (P < 0.01) orthe menstrual cycle (P < 0.001). Corpora lutea atretica (n= 2) and ovarian stroma (n = 6) did not show any EGF bindingactivity. Our findings demonstrate the presence of specificEGF receptors in human corpora lutea of both the menstrual cycleand pregnancy. The changes in EGF binding parameters in earlypregnancy suggest that there may be a relationship between therole of EGF and ovarian steroidogenesis.     

Induction of final follicular maturation and early luteinization in women undergoing ovulation induction for assisted reproduction treatment--recombinant HCG versus urinary HCG. The European Recombinant Human Chorionic Gonadotrophin Study Group

This multicentre, double-blind, double-dummy, randomized, parallel-groupstudy compared the efficacy and safety of recombinant humanchorionic gonadotrophin (rHCG) (Ovidrel^®) and urinary HCG(uHCG) (Profasi^®) for inducing final follicular maturationand early luteinization in women undergoing ovulation inductionfor assisted reproduction treatment. Following long down-regulationand stimulation with recombinant human FSH (rFSH) (Gonal-F^®),a total of 190 women received a single, s.c. injection of either250 µg rHCG or 5000 IU uHCG. For evaluable patients (n= 172), the mean number of oocytes retrieved per patient (primaryefficacy endpoint) was 11.6 for rHCG and 10.6 for uHCG (notsignificant). The mean number of mature oocytes was statisticallyhigher (P = 0.027) for the rHCG group than the uHCG (9.4 versus7.1). Serum progesterone concentrations on day 1 and days 6–7post-HCG, and serum HCG concentrations at all post-HCG timepoints were statistically significantly in favour of rHCG. Theclinical pregnancy rate was somewhat higher (not significant)in the rHCG group (33 versus 25%) as was the live birth rate(27 versus 23%, not significant). Both treatments were welltolerated, though the incidence of adverse events was significantlyhigher in the uHCG group (45.1 versus 22.7%, P = 0.0004). Theincidence of injection-site reactions was significantly lowerin the rHCG group (P = 0.0001). In conclusion, for triggeringovulation, rHCG seems to have significant advantages comparedwith uHCG in terms of number of mature oocytes retrieved, lutealprogesterone and local tolerance.     

A controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization

The outcome of in-vitro fertilization and embryo transfer (IVF—ET)was compared in 76 patients with polycystic ovaries (PCO) diagnosedon pre-treatment ultrasound scan, and 76 control patients whohad normal ovaries and were matched for age, cause of infertilityand stimulation regimen. Despite receiving significantly lesshuman menopausal gonadotrophin (HMG), patients with PCO, ascompared with controls, had significantly higher serum oestradiollevels on the day of human chronic gonadotrophin administration(5940 ± 255 versus 4370 ± 240 pmol/1, P < 0.001),developed more follicles (14.9 ± 0.7 versus 9.8 ±0.6, P < 0.001) and produced more oocytes (9.3 ± 0.6versus 6.8 ± 0.5, P = 0.003). However, fertilizationrates were reduced in the PCO patients (52.8 ± 3.4% versus66.1 ± 3.4%, P = 0.007). There was no significant differencein cleavage rates. The pregnancy rate/embryo transfer was 25.4%in the PCO group and 23.0% in the group with normal ovaries.There were three high order multiple pregnancies in the PCOgroup compared with none in the group with normal ovaries. Ofthe PCO patients, 10.5% developed moderate/severe ovarian hyperstimulationsyndrome (OHSS) compared with none of the controls (P = 0.006).Patients with and without PCO undergoing IVF have comparablepregnancy and livebirth rates. However, it is important to diagnosePCO before ovarian stimulation is initiated as these patientsare more likely to develop moderate or severe OHSS following1VF—ET.     

Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin

To assess the risk of miscarriage after in-vitro fertilization(IVF) with respect to age, cause of infertility, ovarian morphologyand treatment regimen, a retrospective analysis was performedof the first 1060 pregnancies conceived between June 1984 andJuly 1990 as a result of 7623 IVF cycles. Superovulation inductionwas achieved with human menopausal gonadotrophin (HMG) and/orpurified follicle stimulating hormone (FSH) together with eitherclomiphene citrate or the gonadotrophin hormone-releasing hormone(GnRH) agonist buserelin, the latter either as a short ‘flare’regimen or as a ‘long’ regimen to induce pituitarydesensitization. There were 282 spontaneous abortions (26.6%)and 54 ectopic pregnancies (5.1%). The mean age of women withongoing pregnancies was 32.2 (SD 3.9) years compared with 33.2(SD 4.1) years in those who miscarried, which were significantlydifferent (P = 0.008). There was no relation between the miscarriagerate and the indication for IVF. The miscarriage rate was 23.6%in women with normal ovaries compared with 35.8% in those withpolycystic ovaries [P = 0.0038, 95% confidence interval (CI)4.68–23.10%]. There was no difference in the miscarriagerate between treatment with HMG or FSH. Women whose ovarieswere normal on ultrasound were just as likely to miscarry ifthey were treated with clomiphene or with the long buserelinprotocol. Those with polycystic ovaries, however, had a significantreduction in the rate of miscarriage when treated with the longbuserelin protocol, 20.3% (15/74), compared with clomiphenecitrate, 47.2% (51/108) (P = 0.0003, 95% CI 13.82–40.09%).