Endocrine composition of follicular fluid comparing human chorionic gonadotrophin to a gonadotrophin-releasing hormone agonist for ovulation induction

Concentrations of inhibin, oestradiol and progesterone weredetermined in pre-ovulatory follicular fluid from 16 women undergoingin-vitro fertilization and embryo transfer treatment. A prospectiverandomized design was used such that ovulation was induced ineight women with human chorionic gonadotrophin (HCG) (9000 IU),and in eight women with an endogenous surge of luteinizing hormone(LH) and follicle stimulating hormone (FSH) caused by a singleinjection of gonadotrophin-releasing hormone agonist (GnRHa).Inhibin was measured by an enzyme-linked immunosorbent assay,and oestradiol and progesterone were measured by radioimmunoassay.Concentrations of inhibin and progesterone are significantlyhigher in follicular fluids collected after ovulation inductionwith HCG compared with ovulation induction with GnRHa (P <0.001, P < 0.02, respectively). Concentrations of oestradiolwere similar in the two groups. This study shows that the methodby which ovulation is triggered significantly affects the micro-environmentof the oocyte just prior to ovulation. The results indicatethat HCG causes a prolonged luteotrophic effect well beforeovulation, compared to an endogenous surge of gonadotrophinscaused by GnRHa, and suggest that follicular maturation withan endogenous surge of gonadotrophins may be closer to the naturalcycle than those cycles in which HCG is administered for ovulationinduction. In addition, this study shows that the concentrationsof inhibin and progesterone in follicular fluid may be valuableparameters in assessing the midcycle LH surge requirements forinduction of ovulation.     

Luteal support with micronized progesterone following in-vitro fertilization using a down-regulation protocol with gonadotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration.

This study aimed to compare the efficacy of micronized progesterone administered as luteal support following ovulation induction for in-vitro fertilization (IVF)- embryo transfer in cycles using gonadotrophin-releasing hormone agonist, either orally (200 mgx4/day) or vaginally (100 mgx2/day) and to characterize the luteal phase hormonal profile during such treatments. A total of 64 high responder patients requiring intracytoplasmic sperm injection due to male factor infertility were prospectively randomized into two treatment groups. Patients treated orally or vaginally were comparable in age (31.9 +/- 6.1 versus 30.6 +/- 5.2; mean +/- SD), number of oocytes retrieved (17 +/- 8.2 versus 18 +/- 7.0), and number of embryos transferred (3.1 +/- 1.2 versus 2.7 +/- 0.9) per cycle. Following low dose vaginal treatment, a significantly higher implantation rate (30.7 versus 10.7%, P < 0.01), but similar clinical pregnancy rate (47.0 versus 33.3%) and ongoing pregnancy rate (41.1 versus 20.0%) was observed, compared with oral treatment. In conception cycles, luteal serum progesterone and oestrogen concentrations did not differ between the treatment groups. In non-conception cycles, late luteal progesterone concentrations were significantly lower following vaginal treatment. As low dose micronized progesterone administered vaginally is simple, easy and well tolerated, it could be recommended as the method of choice for luteal support, especially for high responder patients at risk for ovarian hyperstimulation syndrome.     

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.     

Effect of antenatal dexamethasone therapy on maternal plasma human chorionic gonadotrophin, oestradiol and progesterone

The aim of this study was to determine whether the current regimen of dexamethasone administration to induce fetal lung maturation affected the circulating concentrations of placental hormone. A standard regimen of dexamethasone that comprised two doses of 12-mg intramuscular injections, 12 h apart was administered to 12 pregnant women to promote fetal lung maturation in anticipation of premature delivery before 34 completed weeks of gestation. Blood samples were collected before starting the dexamethasone therapy, 24 h, and 48 h after completing therapy for the measurement of the plasma concentrations of human chorionic gonadotrophin (HCG), oestradiol and progesterone. There was a progressive fall in the plasma concentrations of HCG following dexamethasone therapy (P = 0.049 and P = 0.034, 24-h and 48-h post therapy respectively). There was an initial fall in the plasma concentrations of oestradiol after dexamethasone therapy (z = 3.059; P = 0.002, 24-h post therapy), which recovered by 48 h (P = 0.239). There was no difference between the plasma concentrations of progesterone at the three time points. The effect of dexamethasone on HCG concentrations suggests that it has a direct inhibitory effect on placental hormone synthesis or secretion. Further studies are needed to define the mechanism of action of dexamethasone on placental HCG production.     

Treatment of normal women with oestradiol plus progesterone prevents the decrease of leptin concentrations induced by ovariectomy

To study the role of oestradiol and progesterone in the secretion of leptin, 21 normally ovulating women were recruited from those scheduled for ovariectomy plus hysterectomy performed in mid-follicular phase of the cycle. Seven of the women were used as controls and received no hormonal treatment post-operatively. Another seven women received oestradiol (oestradiol group) and the remaining seven women received oestradiol plus progesterone (oestradiol plus progesterone group). Serum leptin values showed a temporal but significant increase 24 h after the operation and were significantly correlated with the cortisol and progesterone values, which increased temporarily at 12 h. At that time a marked decline in oestradiol concentrations was seen. After the temporal increase, leptin values in the controls and the oestradiol group decreased significantly up to day 4 (P: < 0.05), while in the oestradiol plus progesterone group they increased (P: < 0.01) and were significantly higher than in the other two groups (P: < 0.05). Body mass index (BMI) was the most important variable accounting for the changes in leptin values post-operatively, but in the oestradiol plus progesterone group progesterone correlated significantly with leptin independently of BMI. These results suggest that progesterone and cortisol can stimulate leptin secretion in women regardless of oestradiol concentrations.     

Progesterone supplementation increases luteal phase endometrial thickness and oestradiol levels in in-vitro fertilization.

Luteal phase supplementation with natural progesterone appears to increase the pregnancy rate in in-vitro fertilization (IVF). The objective of this investigation was to examine the effect of intravaginal progesterone on endometrial thickness and hormonal parameters 7-9 days after embryo transfer. IVF patients receiving progesterone supplementation (Prog +, n = 64), who did not conceive, were compared to patients not receiving progesterone (Prog -, n = 23) because of failed fertilization. These two groups were also compared to 20 women (Preg) who conceived and to 16 women (control) in the mid-luteal phase of natural cycles. Endometrial thickness was greater (P < 0.01) in the Prog + (0.88 +/- 0.04 cm) and Preg (0.92 +/- 0.02 cm) groups compared to the Prog - (0.71 +/- 0.05 cm) and control (0.65 +/- 0.05 cm) groups. Mean luteal phase serum oestradiol levels were also higher (P < 0.05) in the Prog + (1118 +/- 112 pmol/l) and Preg (2267 +/- 757 pmol/l) groups than in the Prog - (574 +/- 70 pmol/l) and control (468 +/- 38 pmol/l) groups. These findings suggest that progesterone supplementation may affect pregnancy rates in IVF by increasing endometrial thickness, thereby enhancing receptivity for implantation. The mechanism through which this effect occurs is unclear but may involve serum oestradiol elevation.     

Concentrations of free oestradiol and progesterone in human preovulatory follicular fluid

This study describes the distribution, based on computer calculations, of the total concentration of oestradiol (E2) and progesterone (P4) between a free and a protein-bound fraction in each of 98 preovulatory follicular fluids (FF). The FFs were obtained from 30 women undergoing in-vitro fertilization--embryo transfer (IVF-ET) treatment. The concentrations of free and total steroid were correlated to oocyte cleavage and establishment of pregnancies. In the FF, 4.3% of E2 was free, 1.5% was bound to sex-hormone-binding-globulin (SHBG), 94.2% to albumin and less than 0.1% was bound to cortisol-binding-protein (CBP). The distribution of P4 in FF was 4.1% free, 5.6% bound to CBP, 90.3% bound to albumin and less than 0.1% was bound to SHBG. These results demonstrate that albumin plays a central role in maintaining the concentration gradient of steroids between the preovulatory FF and the circulation. The concentration of free E2 in fluid from follicles in which the oocyte cleaved was significantly lower in patients who achieved pregnancy (133 +/- 9 nM) (+/- SEM) than in fluid from follicles in which the oocyte cleaved but where the patient did not become pregnant (169 +/- 13 nM: P less than 0.05). Comparing the same two groups, the total concentration of E2 was also significantly lower in FF from patients who became pregnant. By contrast, no such correlation was found for either the free or the total concentrations of P4 in FF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrinology: Luteal phase oestradiol and progesterone levels are stronger predictors than follicular phase follicle stimulating hormone for the outcome of in-vitro fertilization treatment in women with tubal infertility

Basal follicle stimulating hormone (FSH) in a natural cycle,FSH on cycle days 3 and 10 in a domiphene citrate-stimulatedcycle and oestradiol and progesterone area under the curve (AUC)in the luteal phase of the ciomiphene citrate-stimulated cyclewere evaluated as hormonal predictors for the outcome of FVFtreatment in 53 normally cycling women with tubal infertility.The pregnant women had significantly fewer treatment cycles(P < 0.001) and needed fewer ampoules of gonadotrophins (P< 0.001). They also had more oocyte retrievals (P < 0.001),more oocytes per retrieval (P < 0.01), higher fertilizationrate (P < 0.001) and more replaced pre-embryos per replacement(P < 0.01) as compared with non-pregnant women. Significantdifferences were found in FSH concentrations on cycle days 3(P < 0.05) and 10 (P < 0.001) after domiphene citratestimulation and for oestradiol and progesterone AUC in the lutealphase (P < 0.001) between those women who became pregnantand those who did not become pregnant after IVF treatment Lutealoestradiol and progesterone had considerably stronger predictivevalue for the outcome of IVF treatment as compared to basalFSH and domiphene citrate challenge test.     

Lack of placental protein 14 production in pregnancy after frozen embryo transfer, down-regulation of anterior pituitary and administration of exogenous oestradiol and progesterone

The circulating levels of placental protein 14 (PP14) and progesterone were measured in three pregnancies resulting from the transfer of cryopreserved embryos. Two of these women had suppressed ovarian activity as a result of pituitary down-regulation with the luteinizing hormone-releasing hormone agonist (buserelin) prior to treatment with exogenous oestradiol and progesterone. After 14 days of oral oestradiol treatment and if the endometrial thickness was greater than 7 mm, progesterone was given intramuscularly for a further 14 days with embryo transfer on the third day of this treatment. On confirmation of pregnancy by human chorionic gonadotrophin analysis, progesterone administration was altered to transvaginal pessaries for maintenance of adequate progesterone levels and endometrial support. In the two women with ovarian suppression, PP14 levels remained below the 2.5th centile of the normal range for pregnancy. In the third pregnancy, embryo transfer was performed 3 days after a spontaneous luteinizing hormone surge in a normal menstrual cycle. In this pregnancy, PP14 levels were within the normal range. Ultrasonic examination confirmed three normal ongoing singleton pregnancies. These results suggest that the majority of PP14 production in normal pregnancy is under ovarian or anterior pituitary control and that the influence of progesterone is of a secondary nature.     

Endometriosis and human infertility: a new investigation into the role of eutopic endometrium

BACKGROUND: Endometriosis is related to infertility even in the absenceof mechanical alterations of the reproductive tract. Even thoughthe pathogenesis of this phenomenon is still unclear, an impairedendometrial receptivity has been recently suggested. The aimof the present study was to investigate if endometriotic peritonealfluids (EPF) could interfere with endometrial stromal cell (ESC)decidualization and if tumor necrosis factor (TNF)- could beinvolved in the EPF effect. METHODS: Eutopic ESC were isolated from patients with or without endometriosis.ESC were treated with 17β-estradiol 10^–8 M and 6-methyl-17-hydroxyprogesteroneacetate2x10^–7 M for 16 days. In vitro decidualization was morphologicallyand biochemically assessed. We analysed whether ESC decidualizationcould be affected by EPF or peritoneal fluids from control patients(CPF), with or without soluble TNF- receptor 1 (sTNFR-1). RESULTS: Compared with ESC from control patients, eutopic ESC from patientswith endometriosis showed an impaired decidualization. Decidualizationof normal ESC was morphologically normal but biochemically abnormalin the presence of EPF, which was able to decrease the secretionof decidualization markers. sTNFR-1 was able to partially counteractthis effect. CONCLUSIONS: In endometriosis, the milieu surrounding the uterine cavitymay be involved in impaired eutopic ESC decidualization, partiallydue to increased peritoneal levels of TNF-.     

Controlled preparation of the endometrium with exogenous steroids for the transfer of frozen-thawed pre-embryos in patients with anovulatory or irregular cycles

We have reported a 36% pregnancy rate (eight of 22 transfers) with the transfer of cryopreserved-thawed embryos in patients with anovulatory or irregular cycles following a protocol using pituitary suppression with leuprolide acetate after preparation of the endometrium with transdermal E2 and i.m. P. This protocol is simple, easy to follow, and safe and could be used in future for all patients with cryopreserved pre-embryos.     

Endocrinology: Reduced implantation rate associated with a subtle rise in serum progesterone concentration during the follicular phase of cycles stimulated with a combination of a gonadotrophin-releasing hormone agonist and gonadotrophin

Our objective was to assess the effects of subtle increasesin serum progesterone concentration (1.0–2.0 ng/ml) onthe outcome of in-vitro fertilization (IVF), particularly onthe quality of embryos, during the follicular phase of cyclesstimulated with gonadotrophin-releasing hormone agonist (GnRHa)and human menopausal gonadotrophin (HMG). A total of 97 patientsunderwent 116 cycles of IVF and were stimulated with a combinationof HMG and GnRHa. They were divided into two groups: those witha subtle progesterone rise and those with no progesterone rise.The two groups were compared with respect to serum oestradiol,progesterone, immunoreactive luteinizing hormone (I-LH), bioactiveLH (B-LH), and results of IVF. The groups did not differ significantlyin mean age or in total dose of HMG received. On the day thathuman chorionic gonadotrophin was administered, concentrationsof oestradiol and progesterone were significantly higher inthe subtle progesterone rise cycles than in the no progesteronerise cycles. In the no progesterone rise cycles, the percentagesfor embryos beyond the 4-cell stage, grade 1 embryos, and implantationrates were significantly higher than those in subtle progesteronerise cycles. The combination of GnRHa and HMG eliminated anysignificant rise in serum I-LH or B-LH concentration duringthe follicular phase, but did not suppress the subtle rise inprogesterone. These results confirm our previous finding thata subtle progesterone rise adversely affects the outcome ofIVF. It is also suggested that a reduction in embryo qualitymay influence the lower rate of implantation in subtle progesteronerise cycles.     

Effect of ovulation induction on uterine blood flow and oestradiol and progesterone concentrations in early pregnancy

To determine if oestradiol and progesterone concentrations arerelated to uterine blood flow in early pregnancy, we measuredthese hormones at the time of vaginal Doppler ultrasound beforeand after the beginning of intervillous circulation in spontaneouspregnancy (group I), after clomiphene citrate administration(group II), and after clomiphene citrate plus human menopausalgonadotrophin (HMG) administration (group III). Despite largeincreases of oestradiol concentration in groups II (60%) andIII (300%) and of progesterone in groups II (100%) and III (300%),compared with group I, increases in blood flow were modest duringthe first 9 weeks of gestation. Uterine artery flow volume increasedby 20% in group II and 33% in group III (P 0.02); average velocityincreased by 37% in group III (P < 0.003) compared with groupsI and II; vessel diameter increased by 15% in groups II (P <0.025) and III (P < 0.001) compared with group I; and theuterine artery resistance index decreased by 3 to 5% in groupHI (P = 0.004) compared with groups I and II. Serum oestradioland progesterone concentrations were unrelated to the uterineartery resistance index or volume by an analysis of covariance.We conclude that uterine artery blood flow is significantlyincreased during early pregnancyfollowing HMG administration,and that the increase is unrelated to increases in oestradioland progesterone concentrations.     

Endocrinology: Human chorionic gonadotrophin is a better luteal support than progesterone in ultrashort gonadotrophin-releasing hormone agonist/menotrophin in-vitro fertilization cycles

In an attempt to determine the best luteal support in in-vitrofertilization (IVF) cycles treated with gonadotrophin-releasinghormone agonist (GnRHa) and human menopausal gonadotrophin (HMG)by the ultrashort protocol, 60 patients were prospectively randomizedfor either i.m. progesterone or human chorionic gonadotrophin(HCG) luteal support. The two groups did not differ in the meannumber of oocytes retrieved and embryos replaced, nor in themean age of the patients and the amount of HMG used. HCG maintainedhigher levels of oestradiol and progesterone during the lutealphase. Conception rate was significantly higher in the HCG group.We conclude that HCG is superior to i.m. progesterone as lutealsupport in IVF cycles in which GnRHa is used in the ultrashortprotocol.     

Endocrinology: Triggering of ovulation using a gonadotrophin-releasing hormone agonist does not prevent ovarian hyperstimulation syndrome

A total of 24 women with primary or secondary infertility dueto oligo- or anovulation, were treated with human menopausalgonadotrophin (HMG). In 48 cycles, we used a gonadotrophin-releasinghormone agonist (GnRHa) nasal spray (buserelin) to induce apre-ovulatory endogenous luteinizing hormone (LH) surge. In44 cycles, there was a rapid rise of the serum LH concentrationwithin 8 h from the first administration of GnRHa. One patientwith pituitary hypogonadotrophic amenorrhoea showed a weak orno response in four treatment cycles. Conception occurred in10 cycles (pregnancy/cycle (P/C) index = 22.7%), four of whichended in a spontaneous abortion and six of which are ongoingpregnancies. In 27 cycles, there was an increased risk for ovarianhyperstimulation syndrome (OHSS), defined as more than threefollicles 18 mm in diameter and/or serum oestradiol > 1200pg/ml. Three of these treatment cycles gave rise to the developmentof moderate OHSS in the absence of exogenously administeredhuman chorionic gonadotrophin, two being conception cycles.     

Sequential hormonal supplementation with vaginal estradiol and progesterone gel corrects the effect of clomiphene on the endometrium in oligo-ovulatory women

BACKGROUND: We investigated the possibility of correcting the endometrial alterations induced with clomiphene citrate (CC) by vaginal hormonal supplementation (HS) with estradiol (E2) and progesterone gel. METHODS: Oligo-ovulatory women were prospectively randomized into four groups receiving either 50 mg (groups 1 and 2) or 100 mg (groups 3 and 4) of CC from cycle day 3-8. Groups 2 and 4 also received vaginal E2 cream 0.1 mg twice daily from day 8 until the LH surge and vaginal progesterone gel, starting 3 days after ovulation. All participants had an endometrial biopsy performed 10 +/- 1 days after ovulation. RESULTS: All biopsies in the HS groups (2 and 4) showed complete predecidual changes, and were 'in-phase' with findings normally made 10 days post-ovulation (+/- 2 days of clinical dating). However, without HS (groups 1 and 3), only 4/6 and 3/6 biopsies showed predecidual changes in women receiving 50 and 100 mg of CC. CONCLUSION: The addition of vaginal E2 and progesterone to CC ovulation induction regimens normalizes the alterations in endometrial morphology. Hormonal treatment combining vaginal E2 and progesterone may improve endometrial receptivity in CC cycles and ultimately yield higher pregnancy rates.     

Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study

Transfer of frozen–thawed embryos is usually carried outin a natural cycle or in a programmed cycle in which the endometriumis exogenously stimulated following down-regulation of the hypophysis.To analyse the possibility that the programmed cycle for embryotransfer can still be hormonally manipulated without the useof gonadotrophin-releasing hormone agonist (GnRHa) we have conducteda prospective randomized study that compared the outcome offrozen–thawed embryo transfer cycles using micronized17ß-Oestradiol and micronized progesterone preparationswith and without the concomitant use of GnRHa. One hundred andsix patients were randomly divided into two groups. In groupA (53 patients) 4 mg/day of micronized 17ß-oestradiolwas initiated following down-regulation of hypophysis. In groupB (53 patients) oestrogen stimulation started on day 1 of thecycle without prior pituitary down-regulation using a dose of6 mg/day for 7 days. In both groups, micronized progesteronein a dose of 900 mg/day was administered vaginally after atleast 12 days of oestrogen stimulation. Embryo transfer embryotransfer took place 48-72 h thereafter according to the cryopreservedembryonic stage. Overall, none of the patients had any folliculardevelopment and only one cycle in group B had to be cancelledbecause of premature progesterone secretion. The two groupsdid not differ in age (31 ± 5.6 and 31 ± 5.0 years),number of embryos transferred per patient (3.4 ± 1.2and 3.3 ± 1.0), and day of progesterone initiation (15± 2.2 and 15 ± 1.9 for groups A and B respectively).The endometrial thickness on the day of progesterone initiationwas comparable in both groups (11 ± 1.6 and 10 ±1.6 mm for groups A and B respectively). Similarly, the pregnancyrate per embryo transfer and implantation rate in group A (26.4%and 9.5%) were comparable to those of group B (21.1% and 9%).These results indicate that programmed cycles can be successfullyapplied by administering a high dose of micronized 17ß-oestradiolstarting on day 1 of the cycle. Compared to GnRHa programmedcycles, this approach is simpler, more convenient for both thepatient and medical staff, and results in a similar successrate at a lower cost.     

Effect of exogenous progesterone administration on the morphology of normally developing endometrium in the pre-implantation period

The effects on endometrial morphology of a single, intramuscular dose of 100 mg of progesterone administered in the early luteal phase, between days LH + 1 and LH + 6, were studied in a group (n = 8) of normal, fertile subjects by morphometric techniques and transmission electron microscopy. While the dose of progesterone administered consistently resulted in an increase of salivary progesterone concentration to above the upper limit of the reference range, no significant effect on endometrial development was observed; in particular, endometrial development was not advanced.     

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.