Specific sperm defects are differentially correlated with DNA fragmentation in both normozoospermic and teratozoospermic subjects.

A positive effect of selecting spermatozoa under high magnification during intracytoplasmic sperm injection (ICSI) has been described, but a clear explanation has not been given yet. Previous works have shown that high magnification selected spermatozoa have significantly better chromatin status than unselected cells; on the other hand, it has been reported that spermatozoa with no morphological defects can also be negatively associated with embryo quality and pregnancy outcome attributable to DNA fragmentation. The aim of this study was to investigate whether sperm morphology is correlated with DNA fragmentation, both in normozoospermic and teratozoospermic patients. A prospective cohort study involving 32 subjects was recruited over a 3-month period. Spermatozoa were fixed on a slide for TUNEL assay and evaluated using an epifluorescent light microscope equipped with a video monitor. Single TUNEL-positive or -negative cells were evaluated for morphology at ×4400 magnification. Each spermatozoon was then classified according to morphological normalcy or specific defects. The median percentage of typical forms was 11 and 0%, in the normozoospermic and teratozoospermic groups respectively (p = 0.001). In normozoospermic samples, the percentage of TUNEL-positive morphologically normal spermatozoa was 4%. By comparison, spermatozoa showing a vacuolated head or a small non-oval head had a significantly higher incidence of DNA fragmentation in both groups (12 and 13%, 19 and 13% respectively; p < 0.05). In contrast, spermatozoa showing a pyriform head had a DNA fragmentation rate similar to typical forms (3 and 5%, in normozoospermic and teratozoospermic respectively). This study shows that specific defects evaluated in fixed spermatozoa under high-power magnification are more likely to be associated with DNA fragmentation. High-magnification evaluation of spermatozoa can therefore reduce the probability of selecting cells carrying fragmented DNA during ICSI.

Parthenogenetic activation: biology and applications in the ART laboratory.

Parthenogenesis is a reproductive strategy typical of lower species where a female gives birth to offsprings without a paternal contribution. On the contrary, parthenogenesis is not a form of natural reproduction in mammals even if mammalian oocytes, under appropriate stimuli, can undergo to parthenogenetic activation. This review describes the biological mechanisms regulating parthenogenetic activation in mammals and illustrates the fundamental differences between embryos and parthenotes. Ethical, legal and political concerns on the value of human embryos regulate and limit human embryological studies founded on the widespread belief that human embryos should not be created and studied for research purposes only. Based on the differences between parthenotes and embryos the use of parthenogenesis is proposed as an experimental tool to investigate embryo development which may solve many of the ethical concerns associated with the use of human embryos for experimental purposes. Examples of the possible uses of parthenotes in many field of research such as in vitro assays aimed to study some aspects of assisted reproductive technologies (ART), toxicology or stem cell are described and their validity is discussed.

Impact of Italian legislation regulating assisted reproduction techniques on ICSI outcomes in severe male factor infertility: a multicentric survey.

BACKGROUND: In 2004, a law regulating assisted reproduction techniques (ART) was passed in Italy. The new rules allow for the formation and transfer of a maximum of three embryos at one time, whereas embryo selection and embryo storage are prohibited. The aim of this study is to evaluate the impact of these restrictions on ICSI outcome in couples affected by severe male factor infertility. METHODS: Thirteen Italian ART Units were involved in this study. Data were collected on ICSI cycles performed during 2 years before (control group) and 2 years after (study group) the enforcement of the law. Only cases of obstructive azoospermia (OA), non-obstructive azoospermia (NOA) and severe oligoastenoteratozoospermia (OAT) (sperm count

Follicular vascularity is not predictive of pregnancy outcome in mild controlled ovarian stimulation and IUI cycles.

BACKGROUND: Although follicular vascularity has been shown to be a good indicator of oocyte quality in IVF, scant evidence is currently available on the predictive value of this variable in terms of pregnancy rate during controlled ovarian stimulation (COS) and intrauterine insemination (IUI) cycles. METHODS: Three-hundred and eighteen patients who had received mild COS underwent transvaginal ultrasound scan before performing the IUI. Using power Doppler imaging, vascularity of follicles with a mean diameter > or =16 mm was graded into a three grades according to the circumference of the follicle in which flow was identified. When more than one follicle was observed, grading was performed for all of them, and the highest vascularity grade was recorded. RESULTS: Clinical pregnancy rate (number/total) in the low-, medium- and high-grade vascularity groups was 14.1% (14/99), 10.0% (10/100) and 11.8% (14/119), respectively (P = 0.66). Similar results were observed when only monofollicular cycles were considered. CONCLUSIONS: Follicular vascularity does not predict the chance of pregnancy in women undergoing mild COS and IUI cycles.

Comparison of GnRH agonists and antagonists in assisted reproduction cycles of patients at high risk of ovarian hyperstimulation syndrome.

BACKGROUND: During IVF or ICSI cycles, ovarian hyperstimulation syndrome (OHSS) is a major problem. The aim of this prospective, multicentre, comparative study (using historical controls) was to assess the efficacy of a GnRH antagonist protocol in preventing OHSS in selected patients who had experienced OHSS or had been at risk of OHSS in their previous IVF/ICSI attempt. METHODS AND RESULTS: Patients underwent a new cycle where the same gonadotrophin protocol was used [same dose of recombinant FSH (rFSH)] but a different protocol was used for pituitary desensitization: cetrorelix 0.25 mg multiple-dose antagonist instead of GnRH agonist long protocol. Cetrorelix 0.25 mg was administered daily, starting when the leading follicle reached a diameter of 14 mm. In other words, rFSH was administered in the new cycle according to the dosage and the step-up or step-down modalities used during the previous cycle, independently of ultrasound findings and serum estradiol (E(2)) levels. Eighty-seven patients entered the study. Out of the 87 cycles involving GnRH agonists, 49 (56.3%) were cancelled and out of the 87 involving GnRH antagonists 28 (32.2%) were cancelled [McNemar's test; 95% confidence interval (CI) -35.8% to -11.2%; P < 0.001]. After GnRH agonist cycles, we recorded 24 cases of OHSS (18 moderate and six severe; 27.6%), whereas after the GnRH antagonist cycles there were 10 cases of OHSS (nine moderate and one severe; 11.5%) (95% CI-26.4% to -5.7%; P = 0.006). There was a statistically significant reduction in the total number of follicles with a diameter >10 mm (Wilcoxon's test; Z = 6.1; P < 0.001) and of E(2) levels on the day of HCG administration (2538 versus 4322.4 pg/ml; P < 0.001) in the GnRH antagonist cycles versus GnRH agonist cycles. Twenty-nine patients had an embryo transfer in the first cycle (76.3% of oocyte retrievals) and 57 in the cycle using GnRH antagonist (96.6%). This 20.3% difference was also significant (Z-test; 95% CI 6.8-36.0%; P = 0.003). After the antagonist cycles, 18 pregnancies (20.7 per initiated cycle; 31.6% per embryo transfer) were obtained. CONCLUSIONS: Although this study presents some limitations owing to the use of historical controls, our data show a favourable effect of GnRH antagonists in reducing the incidence of OHSS and the number of assisted fertilization cycles cancelled because of the risk of OHSS in high responder patients. As a consequence, GnRH antagonist plus gonadotrophin administration could also increase the percentage of oocyte retrievals and embryo transfers in this high risk group of patients.

The 2004 Italian legislation regulating assisted reproduction technology: a multicentre survey on the results of IVF cycles.

BACKGROUND: The new Italian law, passed in 2004, regulating assisted reproduction technology imposes that no more than three oocytes can be fertilized at one time and that all embryos obtained must be transferred simultaneously. Oocyte cryopreservation is allowed while embryo cryostorage is banned. The aim of this study was to evaluate the clinical impact of these limitations. METHODS: Seven Italian infertility centres were invited to collect data on IVF cycles performed over the first 4 months of application of the new legislation. As a control, all centres provided data on cycles performed in the same solar period, 1 year before. RESULTS: Data from 1861 cycles were obtained, 961 in the pre-law period and 900 in the post-law period. Pregnancy rate per oocyte retrieval and rate of multiple pregnancies in the pre- and post-law periods were 27.0 and 24.2% (P=0.18) and 25.8 and 20.9% (P=0.11) respectively. However, the prohibition to freeze embryos does appear to have markedly reduced the cumulative rate of success. CONCLUSIONS: The rate of success of IVF-ICSI cycles using fresh embryos is not significantly influenced by the new legislation while the prohibition to freeze embryos seems to result in a more relevant impact.

GnRH antagonists and mild ovarian stimulation for intrauterine insemination: a randomized study comparing different gonadotrophin dosages.

BACKGROUND: The precise role of GnRH antagonists in the armamentarium of drugs for stimulation of ovulation associated with intrauterine insemination remains to be clarified. In this study, we have compared two different protocols employing GnRH antagonists in order to determine the lower effective dose of gonadotrophins to use. METHODS: Sixty-six couples with unexplained infertility or moderate male subfertility were recruited. Starting on day 3 of the cycle, 32 patients were randomized to receive 50 IU of recombinant FSH per day, whereas 34 were treated with 50 IU of recombinant FSH on alternate days. Women received the GnRH antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a leading follicle > or =14 mm in mean diameter was visualized, until HCG administration. Insemination was performed 34 h after HCG injection. RESULTS: The regimen with daily recombinant FSH was associated with a lower rate of mono-ovulation (53.3% versus 78.8%, P=0.06) but also with a higher clinical pregnancy rate per initiated cycle (34.4% versus 5.9%, P=0.005). CONCLUSIONS: A protocol of recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and safe regimen for ovulation induction associated with intrauterine insemination.

Does laparoscopic excision of endometriotic ovarian cysts significantly affect ovarian reserve? Insights from IVF cycles.

BACKGROUND: Residual ovarian function after laparoscopic excision of endometriotic ovarian cysts is a major and still unsolved topic. Ultrasonographic evaluation of ovarian response to ovulation stimulation represents a simple yet poorly employed tool to assess residual ovarian function after surgery. METHODS: Data from patients referred for IVF or ICSI between January 2001 and December 2002 were reviewed. Patients were included who previously underwent laparoscopic excision of a monolateral endometriotic ovarian cyst. The operated ovary and contralateral intact ovary were compared in terms of number of follicles with a mean diameter >15 mm at the time of hCG administration. Basal volume of the two ovaries before initiating stimulation was also compared. A paired Student's t-test was used to investigate differences between the two ovaries. RESULTS: In total, 32 patients and 46 cycles were identified. The mean (+/- SD) number of follicles >15 mm was 4.2 +/- 2.5 in the control ovary and 2.0 +/- 1.5 in the previously operated ovary (P < 0.001); this corresponded to a mean reduction of 53% (95% CI 35-72%) but did not seem to be related to the dimension of the excised ovarian cyst. The basal volume of the operated ovaries was also statistically significantly diminished, though this reduction was less relevant. CONCLUSIONS: Excision of endometriotic ovarian cysts is associated with a significant reduction in ovarian reserve. Further studies are required to clarify whether the damage is related to the surgical procedure or to the previous presence of a cyst.

[Peripheral blood stem cell collection in pediatric malignancies: comparison between three mobilizing regimens]. / La raccolta di cellule staminali periferiche nei tumori pediatrici: confronto fra tre sistemi di mobilizzazione.

PURPOSE: The optimal method for PBSC (peripheral blood stem cells) mobilization in pediatric patients is still unknown. The present study was conducted to evaluate the safety of apheresis procedures and to compare the efficacy of three methods of PBSC mobilization. PATIENTS AND METHODS: Our study was performed on 28 pediatric patients (in three groups) with solid tumors at onset or on relapse. In two groups we tried to mobilize PBSC administering CHT (based on Carboplatin with Etoposide in the first group and Cyclophosphamide in the second group) followed by granulocyte colony stimulating factor (G-CSF); in the third group the mobilization regimen was based on G-CSF alone. RESULTS: Forty-nine mobilizations have been performed and a median of 6.5 CD34+ cells x 10(6)/Kg were collected, with a median number of one apheresis for each patient. Using Carboplatin with G-CSF and Cyclophosphamide with G-CSF we collected respectively a median value of 6.75 and 7.3 x 10(6) CD34+ cells/kg. The mobilization method based on G-CSF alone showed to be less effective (median of 4.3 CD34+ cells x 10(6)/kg collected). CONCLUSIONS: In our experience the mobilizing regimens based on Carboplatin or Cyclophosphamide associated with G-CSF resulted both effective and better than the one based on G-CSF alone with a scanty number of apheresis procedures.

Spectral analysis of R-R interval variability by short-term recording in anorexia nervosa.

Subjects with anorexia nervosa (AN) present a number of changes in autonomic system functions, such as thermoregulation, vascular motility, heart rate and rhythm, and blood pressure. We evaluated the changes in the autonomic control of heart rate and blood pressure after postural variation by means of the spectral analysis of R-R interval variability (HRV in 13 female subjects with AN diagnosed on the basis of diagnostic statistical manual (DSM-IV) criteria, a mean age of 25 +/- 5.8 years and a mean body mass index (BMI) of 16.9 +/- 2.6. The controls were 16 healthy female subjects with a mean age of 25 +/- 2.3 years and a normal BMI. The data were statistically evaluated by means of one-way analysis of variance or Student's t test. The high frequency (HF) components of the spectral analysis did not significantly change when passing from clino- to orthostatism in the AN subjects, but there were significant changes in the controls. The changes in the low frequency (LF) components were similar in both groups, but smaller in the AN subjects. However, the difference between the two series was not statistically significant. The variance in the orthostatic R-R intervals recorded in the AN subjects was significantly less than the clinostatic intervals, the intervals recorded in the controls. These results indicate that AN subjects show signs of autonomic dysfunction. The increase in the HF component of the spectral analysis suggests that parasympathetic modulation is abnormally persistent during orthostatism, furthermore, the variability of the R-R intervals indicates that orthosympathetic regulation is also altered in AN.

Comparison of luteal phase profile in gonadotrophin stimulated cycles with or without a gonadotrophin-releasing hormone antagonist.

BACKGROUND: The aim of our study was to explore luteal phase hormone profiles in gonadotrophin-stimulated cycles with or without gonadotrophin-releasing hormone (GnRH) antagonist therapy during intrauterine insemination (IUI). Forty-one infertile couples were recruited in this randomized clinical study. METHODS: The 19 patients included in group A were treated for 21 cycles with recombinant FSH 150 IU/day starting from day 3 of the cycle and with the GnRH antagonist cetrorelix at the dose of 0.25 mg/day starting from the day in which a follicle with a mean diameter of > or =14 mm was seen at ultrasound scan. Cetrorelix was administered until human chorionic gonadotrophin (HCG) administration. The 22 patients included in group B were administered recombinant FSH alone at the same dosage for 27 cycles. RESULTS: The two treatment groups showed a similar increase in progesterone concentration during the luteal phase. In the mid-luteal phase (day 6 after HCG), oestradiol concentrations in group B were significantly higher compared with group A (P < 0.05) but the oestradiol:progesterone ratio was similar in the two groups. Serum LH was completely suppressed during the follicular phase only in group A, concomitantly with GnRH antagonist administration. A total of six pregnancies, all ongoing, were achieved (14.3% per patient and 12.2% per cycle), equally distributed in group A and in group B. CONCLUSION: GnRH antagonists can be safely administered in gonadotrophin-stimulated IUI cycles without luteal phase supplementation because no deleterious effects of GnRH antagonist administration were noted on luteal progesterone concentration or on the duration of the luteal phase.

[Induction of monofollicular cycles]. / Induzione di cicli monofollicolari.

The therapy of anovulatory infertility is not meant to obtain a pregnancy at any cost, but to restore an ovulation as physiological as possible. This involves the use of drugs and therapeutical protocols to obtain monofollicular cycles. Monofollicularity reduces the two main risks of induction of ovulation: ovarian hyperstimulation syndrome and multiple pregnancy. The aim of this study is a review of the Literature on ovulation induction and a comparison with the data of our Sterility Service. The importance of the question will be examined together with the most used ovulation induction drugs: clomiphene citrate, gonadotrophins and pulsatile GnRH. The parameters considered are: the number of follicles, single or multiple pregnancies and ovarian hyperstimulation. After a review about ovarian stimulation, the results of our Sterility Service are presented: 364 cycles of ovulation induction with clomiphene citrate, low-dose gonadotrophins or pulsatile GnRH were monitored; monofollicularity was obtained in 58,48% of ovulatory cycles. Differences between drugs will be described in the text. The therapy of anovulatory infertility aims to restore a physiological ovulation and to obtain a single pregnancy, not a pregnancy at any cost.

Reliability of ovulation tests in infertile women.

OBJECTIVE: To assess the reliability of the most widely used clinical methods for predicting or confirming ovulation. METHODS: We monitored spontaneous cycles in 101 infertile women using basal body temperature (BBT), transvaginal ultrasound, a urinary stick system for LH surge, and three serum progesterone measurements in the midluteal phase. Transvaginal ultrasound monitoring was standard for ovulation detection and sensitivity. We calculated specificity and accuracy of each method compared with that standard. RESULTS: Follicular development and ultrasound evidence of ovulation were confirmed in 97 of 101 cycles (96%). Urinary LH surge preceded follicular rupture assessed by ultrasonography in all cycles and showed concordance with ultrasound-evidenced ovulation in 98 of 101 cases. The timing of BBT nadir had wide variability, and BBT and ultrasonography agreed in a similar percentage of cases (74%). Midluteal serum progesterone assessments showed ovulatory values in 93 subjects, and ovulation was concordant with ultrasonography in 90 subjects. CONCLUSION: Urinary LH was accurate in predicting ovulation with ultrasonography as the standard for detection, but time varied widely. The nadir of BBT predicted ovulation poorly. The BBT chart was less accurate for confirming ovulation, whereas a single serum progesterone assessment in midluteal phase seemed as effective as repeated serum progesterone measures.

Efficacy of double intrauterine insemination in controlled ovarian hyperstimulation cycles.

OBJECTIVE: To investigate the effectiveness of double IUI and to determine the optimal timing of IUI in relation to hCG administration. DESIGN: Prospective randomized study. SETTING: Infertility Center, Department of Obstetrics and Gynecology, University of Milan. PATIENT(S): Patients with male factor and unexplained infertility undergoing controlled ovarian hyperstimulation (COH) and IUI. INTERVENTION(S): After COH with clomiphene citrate and gonadotropins, patients were randomly assigned to one of the following groups: group A received a single IUI 34 hours after hCG administration, group B received a double IUI 12 hours and 34 hours after hCG administration, and group C received a double IUI 34 hours and 60 hours after hCG administration. MAIN OUTCOME MEASURE(S): Number of follicles > 15 mm in diameter on the day of hCG administration, number of motile spermatozoa inseminated, clinical pregnancy rate. RESULT(S): Two hundred seventy-three patients underwent 449 treatment cycles: 90 patients were treated for 156 cycles in group A, 92 patients for 144 cycles in group B, and 91 patients for 149 cycles in group C. The overall pregnancies rates for groups A, B, and C were 13 (14.4% per patient and 8.3% per cycle), 28 (30.4% per patient and 19.4% per cycle), and 10 (10.9% per patient and 6.7% per cycle), respectively. There was a statistically significant difference between group B and groups A and C. CONCLUSION(S): Our data indicate that two IUIs performed 12 hours and 34 hours after hCG administration is the most cost-effective regimen for women undergoing COH cycles with clomiphene citrate and gonadotropins. Although the second insemination adds up to a slightly higher cost, it significantly increases the chance of pregnancy.

Long-term results of an intensive regimen: VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease.

PURPOSE: This pilot study was conducted to evaluate the efficacy and toxicity of a new intensive drug regimen, combined with involved-nodal-field radiotherapy, in advanced Hodgkin's disease not treated by chemotherapy. PATIENTS AND METHODS: From September 1990 to March 1993, 73 evaluable patients with newly diagnosed stage IIB, III (A and B), and IV (A and B) Hodgkin's disease or who were relapsing after primary subtotal or total nodal irradiation were treated with eight cycles of etoposide, epirubicin, bleomycin, cyclophosphamide, and prednisolone (VEBEP) followed by radiotherapy (30-36 Gy) to the nodal site or sites of pretreatment disease. The median duration of follow-up was 68 months. RESULTS: The complete remission rate was 94% (95% CI: 86-98). At 6 years, freedom from progression and overall survival rates were 78% (95% CI: 68-88) and 82% (95% CI: 73-91), respectively. There was one episode of fatal sepsis after bone marrow aplasia that occurred after VEBEP and extended-field irradiation. Hematologic toxicity during chemotherapy was acceptable; without the support of growth factors, grade IV leukopenia and grade IV neutropenia, as determined within cycles, occurred in 38% and 85% of patients, respectively, but was reversible in the vast majority of patients by the day of treatment recycle. No episodes of epidoxorubicin-related cardiomyopathy or symptomatic pulmonary toxicity were documented. Overt and/or subclinical hypothyroidism occurred in 38% of cases. Gonadal damage was evident in the large majority of male patients but reversible in half of them, whereas permanent sterility was observed in females at least 35 years of age. No secondary leukemia has been so far detected. DISCUSSION: VEBEP followed by involved-nodal-field radiotherapy is an effective treatment for chemotherapy-naive Hodgkin's disease and is associated to acceptable rates of acute and intermediate-term toxicity. This intensive regimen, which does not routinely require the support of hematopoietic growth factors and can be delivered in an outpatient setting, warrants a prospective comparison in a randomized trial versus one of the more effective standard-combination regimens.

Endometrial morphology and ultrasound vascular findings. A randomized trial after intramuscular and vaginal progesterone supplementation in IVF.

Luteal-phase supplementation has proved necessary in Gn-RH analog and human gonadotropin-stimulated cycles. We studied the effects of vaginally and intramuscularly delivered progesterone on the endometrium. Thirty patients enrolled in an IVF program without embryo transfer due to absence of fertilization were included in the study. Patients were randomly allocated to two treatment groups. Group A (n = 15) was administered 200 mg progesterone b.i.d. by the vaginal route (Esolut, Angelini) starting on the day of oocyte pick up and group B (n = 15) was given 100 mg intramuscular progesterone once daily (Prontogest, Amsa). Six days after HCG administration, biopsies were obtained for endometrial histological maturation and estrogen (ER) and progesterone (PR) receptor analyses. In addition, ultrasound measurements of endometrial thickness were made and uterine and myometrial artery flow was determined. Serum concentrations of estriol and progesterone were measured on the day of HCG, at oocyte pick up and at endometrial biopsy. The two treatment groups were similar in terms of follicular phase parameters during superovulation with Gn-RH analog and gonadotropin. Histologic, receptor and ultrasonographic analyses showed no significant differences between the two treatment groups. Our results indicate that both intramuscular and vaginal progesterone are equally effective on the endometrium.

Semen preparation by standard swim-up versus swim-up with test yolk buffer incubation in intrauterine insemination: a randomized study.

In order to compare the standard swim-up semen preparation with and without test yolk buffer (TYB) incubation in intrauterine insemination (IUI), we conducted a prospective multicentre randomized trial. A total of 121 infertile couples with male factor (n = 52) or unexplained infertility (n = 69) was randomly assigned to two groups following ovulation induction. Semen was prepared by standard swim-up in group A (n = 64) and by swim-up followed by TYB incubation in group B (n = 57). A maximum of two IUI cycles was performed. A total of 104 cycles was performed in the swim-up group and 90 in the TYB group. Overall, 15 pregnancies were achieved in group A and 23 in group B, with an overall pregnancy rate of 24.8 and 50.0% per patient respectively (chi2(1), P < 0.05). In the male factor group, pregnancy was achieved in six out of 24 couples (25%) following standard swim-up and in six out of 28 (21.4%) following swim-up and TYB incubation (chi2(1), not significant). In the unexplained infertility group, pregnancy was recorded in nine out of 40 couples (22.5%) following standard swim-up and in 17 out of 29 couples (58.6%) following swim-up and TYB incubation (chi2(1), P < 0.05).

Ovarian stimulation with low-dose pure follicle-stimulating hormone in polycystic ovarian syndrome anovulatory patients: effect of long-term pretreatment with gonadotrophin-releasing hormone analogue.

A randomised clinical trial was performed to evaluate the effect of a 3-month gonadotrophin-releasing-hormone analogue (GnRH-a) in one cycle of ovulation induction with low-dose pure follicle-stimulating hormone (pFSH) in patients with polycystic ovarian syndrome (PCOS) anovulation. Twenty patients with chronic anovulation due to PCOS were randomised to ovulation induction with pFSH administered in a low-dose schedule with (10 patients) and without (10 patients) a 3-month pretreatment with GnRH-a. Ultrasound scan only monitoring of follicular growth, evaluation of plasmatic oestradiol at the day of triggering of ovulation with human chorionic gonadotrophin 5,000 IU and evaluation of plasmatic progesterone 8 days after were the main outcome measures. Ovulation occurred in 9 patients treated with pFSH and in 2 patients treated with GnRH-a plus pFSH. Five pregnancies in the pFSH group and no pregnancy in the GnRH-a group were obtained. Five cycles were stopped due to multifollicular growth in the GnRH-a group and 1 in the pFSH group. Pretreatment with a 3-month administration of a GnRH-a did not improve the ovulation rate and pregnancy rate in PCOS patient ovulation induction with low-dose pFSH.