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.     

In-vitro fertilization and the ovarian hyperstimulation syndrome.

Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.     

Serum and follicular resistin levels in women with polycystic ovarian syndrome during IVF-stimulated cycles

BACKGROUND: Resistin is a hormone linking obesity and insulin resistance. The aim of this study was to compare resistin levels in serum or follicular fluid from women with polycystic ovarian syndrome (PCOS) and controls, both of whom were undergoing IVF. METHODS: We compared serum and follicular resistin levels in 21 PCOS women and in 18 healthy, normal ovulation, age- and body mass index (BMI)-matched non-PCOS women undergoing IVF. Correlations between serum or follicular fluid resistin levels and reproductive outcome were evaluated. RESULTS: There was no significant difference in either serum or follicular resistin levels between the control group and the PCOS group as a whole or those with insulin resistance [homeostasis model assessment of insulin resistance index applied to oral glucose tolerance test (HOMA(OGTT)) <4.7]. However, resistin levels in follicular fluid were unexpectedly significantly lower than serum levels (P<0.0001) in both the PCOS and control groups. No significant correlation was found between resistin levels and BMI, estradiol, LH, or fasting or 2 h glucose or insulin levels or between follicular resistin levels and fertilization rate, implantation rate, clinical pregnancy rate, or early miscarriage rate in PCOS. CONCLUSION: Resistin is unlikely to be a major determining factor in the growth and maturation of oocytes during IVF-stimulated cycles in PCOS.     

Revisiting the ovarian volume as a diagnostic criterion for polycystic ovaries

BACKGROUND: This study revisited the ovarian volume (OV) as a diagnostic criterion for polycystic ovaries (PCO). Indeed, a threshold of 10 cm(3) for the OV, chosen at the polycystic ovary syndrome (PCOS) international consensus held at Rotterdam in 2003, was to date not based on appropriate studies such as receiver operator characteristic (ROC) curve analysis. METHODS: This prospective study included 154 women with PCOS, selected by using the former National Institutes of Health criteria, who were compared with 57 women with normal ovarian function. Ultrasound examination was performed between cycle days 2 and 7 with a 7 MHz transvaginal transducer. RESULTS: Mean OV, ovarian area (OA) and follicle number (FN) values were significantly higher in the PCOS group than in controls. The area under the ROC curve (AUC) was >0.9 for all three criteria, indicating a satisfactory diagnostic potency for each. Concerning the OV, setting the threshold at 7 cm(3) offered the best compromise between specificity (91.2%) and sensitivity (67.5%). In comparison, specificity and sensitivity were 98.2 and 45%, respectively, with a threshold at 10 cm(3). Nevertheless, the highest AUC was obtained for FN (0.956) and then for OA (0.941). CONCLUSIONS: OV is a good diagnostic criterion for PCO but, on the basis of the present data, we propose to lower its threshold to 7 cm(3). The FN >12 still appears as the best diagnostic criterion. The OA could be used as a surrogate for OV in difficult situations.     

In-vitro fertilization in infertile women with the polycystic ovarian syndrome

Forty-four infertile patients with the polycystic ovarian syndrome (PCOS) resistant to other treatment modalities were treated in 58 cycles of IVF after accomplishment of pituitary gonadotroph suppression with a GnRH-agonist. Four cycles were cancelled before oocyte retrieval while embryo transfer was deferred for 10 cycles due to imminent ovarian hyperstimulation syndrome (OHSS). Follicle aspiration yielded 18.8 +/- 9 oocytes per cycle. The cleavage rate was 68%. There was no cleavage in five cycles. The pregnancy rate was 33.3% per embryo transfer. In 32 cycles 9.0 +/- 5 suitable supernumerary embryos were cryopreserved. Transfer of cryopreserved embryos gave three additional pregnancies. The accumulated pregnancy rate per patient was 36%. In clomiphene citrate resistant patients, transfer of cryopreserved embryos was accomplished after secretory transformation of the endometrium by oestradiol/progesterone substitution. Although seven pregnancies ended in a miscarriage, the 'take-home' baby rate was 20%. OHSS ensued in 28 (46.7%) cycles. In PCOS, in-vitro fertilization following pituitary gonadotroph suppression seems a treatment alternative with pregnancy rates comparable to normo-ovulatory women with tubal factor infertility. However, the incidence of OHSS is high and constitutes the major problem of cycle control.     

Growth hormone response to thyrotrophin releasing hormone in women with polycystic ovarian syndrome.

Recent clinical studies have suggested that women with polycystic ovarian syndrome (PCOS) may have disturbances of growth hormone (GH) kinetics and the GH/insulin-like growth factor (IGF)-I system. The knowledge that in various metabolic abnormalities there is a paradoxical sensitivity of pituitary somatotrophs to thyrotrophin releasing hormone (TRH) administration led to this investigation of the GH secretory response to TRH in women with PCOS. Twenty-four women with PCOS and 18 control women were studied. TRH was given as a single i.v. injection (time 0) and blood samples for GH measurements were obtained at -15, 0, 15, 30, 60 and 90 min. The GH responses were expressed as the area under the curve (AUC) or the differences from the basal value (Deltamax). The GH response to TRH (mean +/- SEM) was greater in women with PCOS (Deltamax 2.47 +/- 1. 73 versus 0.47 +/- 0.06 ng/ml, P < 0.05 and GH AUC 8.05 +/- 2.10 versus 2.58 +/- 0.18 ng/ml/90 min, P < 0.05). According to GH response to TRH, two PCOS subgroups were identified: (i) normal responders (n = 14) who showed Deltamax GH response (0.36 +/- 0.06 ng/ml)and GH AUC (1.93 +/- 0.64 ng/ml/90 min) similar to that in the controls and (ii) over-responders (n +/- 10) who showed a paradoxical increase in GH concentrations in response to TRH (Deltamax GH response 5.43 +/- 1.27 ng/ml and GH AUC 16.62 +/- 3.51 ng/ml per 90 min) that was significantly higher than in normally responding PCOS patients (P < 0.0001) or in controls (P < 0.0001). These data demonstrate an enhanced GH response to TRH administration in a subgroup of women with PCOS.     

Laparoscopic ovarian diathermy in women with polycystic ovarian syndrome: a retrospective study on the influence of the amount of energy used on the outcome

BACKGROUND: Currently, there is an uncertainty about the optimum number of punctures to be applied at laparoscopic ovarian diathermy (LOD). This retrospective study was undertaken to investigate the dose-response relationship of LOD. METHODS: The hospital records of 161 women with polycystic ovarian syndrome who underwent LOD were reviewed and the clinical data before and after LOD were documented. Subjects were divided into six groups according to the number of punctures made in their ovaries as follows: group 1, two punctures per ovary; group 2, three punctures; group 3, four punctures; group 4, five punctures; group 5, six punctures and group 6, seven to 10 punctures. Contingency table analysis and analysis of variance were used to compare the outcomes of the different groups. RESULTS: The rates of ovulation, conception and restoration of menstrual regularity after LOD were significantly lower in group 1 compared with other groups. There were no significant differences in the success rates between the other groups. CONCLUSION: Two punctures per ovary are associated with poor results. Three punctures per ovary seem to represent the plateau dose. The application of seven or more punctures per ovary may result in excessive destruction to the ovary without any improvement of the results and should therefore be discouraged.     

Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome

BACKGROUND: Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. METHODS: The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. RESULTS: The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. CONCLUSIONS: Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.     

Vascular endothelial growth factor levels in serum and plasma from patients undergoing controlled ovarian hyperstimulation for IVF

BACKGROUND: Vascular endothelial growth factor (VEGF) has been investigated as a marker of ovarian response to controlled ovarian hyperstimulation and as a predictor of ovarian hyperstimulation syndrome (OHSS) in IVF cycles. In most studies, serum has been used for circulating VEGF concentration measurement, but it has been suggested that plasma is the preferred medium to measure VEGF levels because of the potential contribution of VEGF released from platelets during blood clotting. This study investigated VEGF concentrations in paired serum and plasma samples from patients undergoing controlled ovarian hyperstimulation for IVF. METHODS: Serum and plasma VEGF levels, as well as the number of platelets, were measured in 30 IVF patients who comprised three study groups delineated according to the estradiol (E(2)) serum concentration reached on the day of HCG administration: 10 patients having low E(2) serum levels (<1500 pg/ml, group L), 10 patients having intermediate E(2) serum levels (1500-3000 pg/ml, group I) and 10 patients having high E(2) serum levels (>3000 pg/ml, group H). RESULTS: There was a statistically significant correlation between plasma and serum VEGF levels (rho = 0.61; P < 0.005) for the entire population studied, although serum values were higher by a factor of approximately 6-fold. No significant correlation was found between peripheral blood VEGF concentrations and serum E(2) or follicle number on HCG day or the number of oocytes collected. Similarly, paired serum and plasma VEGF measurements did not correlate with platelet count. CONCLUSIONS: Serum and plasma VEGF concentrations are strongly correlated in paired samples from infertile patients undergoing controlled ovarian hyperstimulation. However, neither serum nor plasma VEGF levels were correlated with parameters associated with ovarian follicular activity. Peripheral blood VEGF levels were not correlated with platelet count.     

Relationships between the serum levels of soluble leptin receptor and free and bound leptin in non-pregnant women of reproductive age and women undergoing controlled ovarian hyperstimulation

BACKGROUND: The aim of this study was to investigate the relationships between the serum levels of soluble leptin receptor (SLEPR), and total, free and bound leptin, and the change in the serum SLEPR level during an IVF cycle. METHODS: Serum concentrations of leptin and SLEPR were measured in 50 Japanese women of reproductive age, and 20 patients participating in an IVF programme. The total leptin was fractionated into free and bound portions by gel filtration chromatography. RESULTS: The SLEPR level was negatively correlated with the body mass index (BMI) (r = -0.548, P < 0.0001), total leptin (r = -0.433, P < 0.0001), the percentage of free leptin (r = -0.732, P < 0.0001) and the absolute free leptin concentration (r = -0.506, P < 0.0001). The SLEPR level was positively correlated with the percentage of bound leptin (r = 0.730, P < 0.0001), whereas there was little variation in the absolute bound leptin concentration, regardless of the BMI or SLEPR concentration. During the IVF cycle, total and free leptin elevated during maximal ovarian stimulation, whereas there was no significant difference in the SLEPR concentration. CONCLUSIONS: The results demonstrate a skillful mechanism where a change in the serum SLEPR level regulates, in part, the biological activity of leptin in the circulation.     

Assessment of ovaries by magnetic resonance imaging in patients presenting with polycystic ovarian syndrome

The demonstration of bilaterally enlarged ovaries with multiple small cysts at ultrasound is the morphological hallmark of polycystic ovarian syndrome (PCOS). However, a number of patients with clinical and biochemical diagnosis of PCOS have ovaries that are without sonographically visible discrete cysts. A better contrast resolution is obtained with magnetic resonance imaging (MRI) and enables visualization of organ structure not seen with other techniques. The purpose of the study was to relate the clinical and biochemical features of 10 patients presenting with a PCOS profile to magnetic resonance imaging and to compare these findings with those observed at ultrasound. With MRI, at least one ovary typical of PCOS could be visualized in eight patients, while this was the case in only three patients with ultrasound. The ultrasound examinations were indeed equivocal in the majority of patients (seven cases). No apparent relationship could be found between the clinical and biochemical parameters and ovarian morphology assessed by MRI or ultrasound. In summary, the present study supports the superiority of MRI technique to assess ovarian morphology over the ultrasound technology used in our study. However, the recent technological advances in ultrasound, and specifically the advent of high frequency transvaginal sonography, will be of particular interest in the study of PCOS.     

Luteal phase progesterone excretion in ovulatory women with polycystic ovaries

BACKGROUND: Various studies have reported a prevalence of polycystic ovaries (PCO) of approximately 20% in the 'normal' population. Our aim was to investigate the frequency of ovulation and pattern of luteal phase progesterone secretion in a group of women with PCO who reported regular cycles and in whom ovulation had been established on the basis of previous investigations. METHODS: Subjects collected early morning urine samples for pregnanediol-3-glucuronide measurement from day 10 of the cycle to day 1 of their next menses. Results in three consecutive cycles from women with PCO (group 1, n = 10 and 29 for patients and cycles respectively) were compared with results from two groups with normal ovaries; with either infertility (group 2, n = 10 and 30) or proven fertility (group 3, n = 6 and 19). RESULTS: There were considerable variations in cycle length. The median (range) was group 1: 28 (23-47); group 2: 26 (21-36) and group 3: 27 (25-38) days with more short cycles in both infertile groups. There was more variation in pregnanediol:creatinine in the normal-ovary infertile and PCO groups than in the fertile controls. Levels were higher in the early luteal phase in the fertile normal group than in either infertile group, and the mid-luteal phase peak was lower in the infertile women with normal ovaries. In summary, there was greater variability in luteal phase pregnanediol:creatinine ratios in the PCO and infertile normal-ovary groups than in women with normal ovaries and proven fertility. CONCLUSION: Women with PCO did not have more variation in cycle length than fertile women with normal ovaries, but there were significantly lower levels of progesterone in the early luteal phase. This may contribute to the delay in conception in these patients.     

Gonadotrophin-releasing hormone agonist and ovarian hyperstimulation syndrome in assisted reproduction

The available literature concerning the association betweengonadotrophin-releasing hormone agonist and ovarian hyperstimulationsyndrome has been reviewed and the different patterns by whichthis agent may contribute to the development of such iatrogeniccomplication has been elicited, and guidelines have been presentedfor prevention of this malady. Gonadotrophin-releasing hormoneagonist acts directly on human granulosa cells, probably inits own dose-dependent manner. The extent of this action isprobably subjected to follicular maturation stage and to thedegree of gonadotrophin pre-treatment. Various agonist effectsin assisted reproduction may be implicated in the developmentof ovarian hyperstimulation syndrome: a higher amount of menotrophin;premature luteinization prevention; ‘flare-up’ effect;and a higher pregnancy rate. Different methods for preventionof ovarian hyperstimulation syndrome may be attempted: (i) allembryo cryopreservation with luteal phase reinitiation of agonist;(ii) avoidance of ovulatory human chorionic gonadotrophin (HCG)and continuation of agonist; (iii) cancellation of ovulatoryHCG, prolongation of agonist and later recommencement of menotrophin;(iv) pre-ovulatory LH surge triggering by agonist instead ofthe conventional HCG. Gonadotrophin-releasing hormone agonistmay affect the steroidogenic ovarian stroma directly and suchinteraction may aggravate the development of ovarian hyperstimulationsyndrome.     

Endocrinology: Ultrasonographic appearance of polycystic ovaries is associated with exaggerated ovarian androgen and oestradiol responses to gonadotrophin-releasing hormone agonist in women undergoing assisted reproduction treatment

While no single biochemical test is diagnostic of polycysticovary syndrome (PCOS), most patients show a characteristic ovarianultrasonographic appearance. It has been proposed that a dysfunctionof cytochrome P-450c17 in PCOS leads to an increased 17-hydroxyprogesterone(17-OHP) response to a gonadotrophin-releasing hormone (GnRH)agonist-induced gonadotrophin rise. We postulated that thisabnormality of steroid metabolism might influence the ovarianresponse during assisted reproduction treatment. We investigated106 patients undergoing a short ’boost‘ stimulationregimen for assisted reproduction treatment, including in-vitrofertilization and gamete intra-Fallopian transfers. The ovarianultrasound pattern was correlated with serum testosterone, 17-OHP,androstenedione and oestradiol responses, and with the clinicaloutcome. Polycystic ovaries, defined ultrasonographically asthe presence of 10 follicles between 2 and 10 mm diameter ineither ovary, were found in 48% of the whole study population.Dexamethasone was given to suppress adrenal androgen secretion.Functional ovarian hyperandrogenism (FOH) was defined as serumtestosterone >0.5 nmol/l after dexamethasone. There was asignificantly (P < 0.001) higher prevalence of FOH in patientswith polycystic ovaries (23%) compared with normal ovaries (7%).Patients with polycystic ovaries had approximately double the17-OHP, androstenedione and oestradiol responses to a GnRH agonistas patients with non-polycystic ovaries. Exaggerated 17-OHPand oestradiol responses to GnRH agonist were found in 89% ofpatients with clinically diagnosed PCOS. The number of oocytesretrieved was positively correlated (r = 0.51, P < 0.001)with the oestradiol responses in all patients. Although therewas no difference in the total amount of follicle stimulatinghormone (FSH) used between the patients with polycystic andnormal ovaries, the median peak oestradiol concentration was1.6 times and the oocyte yield 2.3 times greater in patientswith polycystic ovaries. The overall pregnancy rate per transferwas 32% and did not differ between patients with or withoutpolycystic ovaries and FOH. No pregnancies occurred when thebaseline FSH concentration was >10 IU/l. We conclude thatthe ultrasonographic changes characteristic of polycystic ovariesshould be sought in all women undergoing assisted reproductiontreatment.     

Implications of ultrasonically diagnosed polycystic ovaries. I. Correlations with basal hormonal profiles.

The incidence of ultrasonically diagnosed polycystic ovaries (PCO) was studied in 389 Arab patients with different types of menstrual dysfunction and 100 normal women with regular menstruation. Two-hundred-and-forty-six patients (63.2%) were found to have PCO but only 206 (53.0%) were confirmed as cases of polycystic ovarian disease (PCOD) on endocrine grounds. Polycystic ovaries were diagnosed in 50% of patients with hyperprolactinaemia, 36.4% with hypothyroidism, 23.7% with hypothalamic dysfunction, 100% with adrenal 21-hydroxylase deficiency and in 16.0% of normal women. More women with PCOD presented with oligomenorrhoea or dysfunctional uterine bleeding (77.7%) and hirsutism (72.3%) but obesity had no discriminating value between the groups with different diagnoses. Ultrasonic diagnosis of PCO should be supplemented with an endocrine biochemical assessment to prevent overdiagnosis of PCOD and to exclude other endocrine dysfunctions.     

Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries

BACKGROUND: Insulin resistance and hyperinsulinaemia are well-recognized characteristics of anovulatory women with polycystic ovary syndrome (PCOS) but, paradoxically, steroidogenesis by PCOS granulosa cells remains responsive to insulin. The hypothesis to be tested in this study is that insulin resistance in the ovary is confined to the metabolic effects of insulin (i.e. glucose uptake and metabolism), whereas the steroidogenic action of insulin remains intact. METHODS: Granulosa-lutein cells were obtained during IVF cycles from seven women with normal ovaries, six ovulatory women with PCO (ovPCO) and seven anovulatory women with PCO (anovPCO). Mean body mass index was in the normal range in all three groups. Granulosa-lutein cells were cultured with insulin (1, 10, 100 and 1000 ng/ml) and LH (1, 2.5 and 5 ng/ml). Media were sampled at 24 and 48 h and analysed for glucose uptake, lactate production and (48 h only) progesterone production. RESULTS: Insulin-stimulated glucose uptake by cells from anovPCO was attenuated at higher doses of insulin (100 and 1000 ng/ml) compared with that by cells from either ovPCO (P=0.02) or controls (P=0.02). Insulin and LH stimulated lactate production in a dose-dependent manner, but insulin-dependent lactate production was markedly impaired in granulosa-lutein cells from anovPCO compared with either normal (P=0.002) or ovPCO (P<0.0001). By contrast, there was no difference in insulin-stimulated progesterone production between granulosa-lutein cells from the three ovarian types. CONCLUSIONS: Granulosa-lutein cells from women with anovPCOS are relatively resistant to the effects of insulin-stimulated glucose uptake and utilization compared with those from normal and ovPCO, whilst maintaining normal steroidogenic output in response to physiological doses of insulin. These studies support the probability of a post-receptor, signalling pathway-specific impairment of insulin action in PCOS.     

Intrauterine insemination and controlled ovarian hyperstimulation in cycles before GIFT

We have combined intrauterine insemination (IUI) and controlledovarian hyperstimulation (COH), for the treatment of infertilitydue to different aetiologies, prior to performing GUT. To date,we have treated 186 patients over a total of 489 cycles. Themean age of the patients was 34.1 ± 4 years and the meanduration of infertility was 4.8 ± 2.8 years. Folliculardevelopment was induced with human menopausal gonatrophin (HMG).Patients were monitored using serum oestradiol determinationsand ovarian ultrasound. Two intrauterine inseminations wereperformed 12 and 36 h after HCG injection. Semen samples wereprepared utilizing one of two techniques, swim-up or Percollgradient. A total of 33 pregnancies have occurred, the grosspregnancy rate being 17.7% per patient and 6.7% per cycle. Thecumulative pregnancy rate was 30%. Thirty-one pregnancies (94%)occurred within the first four cycles of treatment. During thesame period of time, the pregnancy rate per cycle in patientstreated with gamete intra-Fallopian transfer (GIFT) was 32.9%.Our data suggest that IUI combined with COH can result in pregnancyin a significant proportion of patients, but that the efficiencyper cycle of the technique is significantly lower than GIFT.     

Induction of pre-ovulatory luteinizing hormone surge by gonadotrophin-releasing hormone agonist for women at risk for developing the ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a major risk inpatients undergoing ovulation induction protocols. Withholdinginjection of human chorionic gonadotrophin (HCG) may preventthe development of OHSS, but can also result in failure to ovulateand conceive. We have used a gonadotrophin-releasing hormoneagonist (GnRHa) as an alternative to HCG in women not undergoingin-vitro fertilization in an attempt to prevent OHSS. The studyincluded 12 cycles in 12 women scheduled for ovulation inductionwith human menopausal gonadotrophin (HMG) who were at risk ofdeveloping OHSS (oestradiol>3500 pg/ml, number of follicles>20).GnRHa was injected to induce the pre-ovulatory, luteinizinghormone surge which triggers follicular maturation. Progesteronewas administered for luteal support. Six pregnancies were achieved,and none of the 12 women developed OHSS. Since the pregnancyrate in this study was acceptable, we can recommend the useof GnRHa instead of HCG in any case at risk of developing OHSS     

Ovulation induction using laparoscopic ovarian drilling in women with polycystic ovarian syndrome: predictors of success

BACKGROUND: Although laparoscopic ovarian drilling (LOD) hasbeen widely used to induce ovulation in women with polycysticovarian syndrome (PCOS), predicting the clinical response tothis treatment remains to be elucidated further. This studywas carried out to identify factors that may help to predictthe outcome of LOD. METHODS: This retrospective study included200 patients with anovulatory infertility due to PCOS who underwentLOD between 1990 and 2002. The influence of the various patients'pre-operative characteristics on the ovulation and pregnancyrates after LOD was evaluated. In addition, women were dividedinto two or three categories according to the severity of eachof the various clinical and biochemical parameters of PCOS.The success rates were compared between the categories of eachfactor using contingency table analyses. Multiple logistic regressionanalysis was used to identify independent predictors of successof LOD. RESULTS: Women with body mass index (BMI) 35 kg/m²,serum testosterone concentration 4.5 nmol/l, free androgen index(FAI) 15 and/or with duration of infertility >3 years seem tobe poor responders to LOD. In LOD responders, serum LH levels>10 IU/l appeared to be associated with higher pregnancy rates.CONCLUSION: Marked obesity, marked hyperandrogenism and/or longduration of infertility in women with PCOS seem to predict resistanceto LOD. High LH levels in LOD responders appear to predict higherprobability of pregnancy.     

Luteal estradiol pre-treatment coordinates follicular growth during controlled ovarian hyperstimulation with GnRH antagonists

BACKGROUND: The purpose of this study was to investigate whether luteal estradiol (E(2)) administration reduces follicular size discrepancies and enhances ovarian response in recombinant FSH (r-FSH)/GnRH antagonist protocols. METHODS: We studied prospectively 90 IVF-embryo transfer (ET) candidates who were randomly pre-treated with 17beta-E(2) (4 mg/day) from day 20 until next cycle day 2 (E(2) group, n = 47) or served as controls (control group, n = 43). On day 3, all women started r-FSH treatment. A single 3 mg dose of GnRH antagonist was administered eventually according to follicular maturation. Outcome measures were magnitude of size discrepancy of growing follicles on day 8 of r-FSH treatment and number of follicles >or=16 mm in diameter on the day of HCG. RESULTS: On day 8, follicles were smaller (9.9 +/- 2.5 versus 10.9 +/- 3.4 mm, P < 0.001) and their size discrepancies attenuated (P < 0.001) in the E(2) group compared with the control group. This was associated with more >or=16 mm follicles, mature oocytes and embryos in the E(2) group. CONCLUSIONS: Luteal E(2) administration reduces the pace of growth, improves size homogeneity of antral follicles on day 8 of r-FSH treatment and increases the number of follicles reaching maturation at once. Coordination of follicular development optimizes ovarian response to r-FSH/GnRH antagonist protocols and may constitute an attractive approach to improving their outcome.