Ovulation Induction Protocols Research Articles

Metformin Usage in PCOS Patients Undergoing IVF Does Not Improve Outcome When Utilizing a Dual Suppression Stimulation Protocol

OCP/ GnRH-agonist dual suppression combined with low-dose gonadotropin therapy has been shown to safely and effectively induce ovulation for IVF in PCOS patients. There is increasing data demonstrating the role of metformin for ovarian stimulation. The objective of this study was to review our IVF outcome during treatment with the dual suppression low-dose gonadotropin protocol in PCOS patients comparing those treated with or without metformin. Retrospective review of PCOS patients undergoing IVF evaluating the efficacy of Metformin when added to the dual suppression protocol. We studied patients with PCOS undergoing IVF-embryo transfer with the dual suppression protocol consisting of OCP pretreatment prior to GnRH-agonist suppression and low dose gonadotropin stimulation (no more than 3 ampules) during a four year period (1999-2003). Standard step-down techniques were utilized. A clinical pregnancy was defined as the presence of fetal cardiac activity. An ongoing pregnancy was defined as a pregnancy greater than 20 weeks of gestation. Statistical analysis included Chi-square analysis and non-parametric testing as appropriate. A total of 247 IVF cycles utilizing the OCP- GnRH-agonist- low dose gonadotropin protocol were started. The mean age of patients was 32.7±3.8 years, and the mean body mass index was 24.9±5.3. Of those that were cancelled prior to retrieval(13/247, 5.3%), 6 (46.2%) were cancelled due to poor response, and 7 (53.8%) were cancelled due to drop in serum E2 level. 221 patients underwent a transfer. Of the cycles that did not proceed with ET, 2 cycles (15.4%) were aborted due to hyperstimulation risk, and embryos were cryopreserved. The mean implantation rate was 37.9%. Overall the positive pregnancy rate , clinical pregnancy rate, and ongoing pregnancy rate per ET were 75.6%, 68.3% and 59.3%, respectively. In 43 cycles (17.4%), patients were treated with metformin. These patients had a higher mean BMI (p<.001) than those not treated with metformin. Cycles in which patients were treated with metformin did not differ significantly from those in which patients were not treated with metformin in terms of outcomes such as maximum E2, number of oocytes retrieved, number of fertilized embryos and number of embryos transferred. Cycles in which patients were treated with Metformin required more ampules of gonadotropins than those in which patients were not treated with Metformin (23.9±8.1 vs. 21.2±8.0, p<.05). However, when corrected for BMI, there was no difference in number of ampules required. Tabled 1 We have demonstrated a successful ovulation induction protocol of PCOS women undergoing IVF. The addition of Metformin did not appear to improve outcome parameters. Further work is required to elucidate the value of Metformin in IVF stimulation utilizing the OCP- GnRH-agonist- low dose gonadotropin protocol.

Novel Stimulation Protocol to Reduce ART Cost Without Compromising Pregnancy Outcome

ObjectiveTo evaluate the effectiveness of a low cost novel ovulation induction protocol for IVF/ICSI.DesignProspective study.Materials and methodsForty non insuline resistant infertile patients underwent IVF/ICSI during August and September of 2004.Twenty out of forty patients received 40 μg of leuprolide acetate twice a day and 650 mg of metformin, starting the first day of the ART cycle until hCG administration. On day two the ovulation induction began with 60 mg of tamoxifen per day during four days associated with low doses of urinary gonadotrophin therapy (Group I). Twenty patients were assigned as the control group (Group II). They received leuprolide acetate 1 mg/day from the midluteal phase of the previous cycle in association with recombinant FSH (300 IU/day during the first four days of the treatment cycle) in a step down protocol. The variables analyzed included age, International Units (IU) of gonadotrophins, stimulation length, stimulation cost (U$S), number of oocytes retrieved,number of embryos transferred, implantation rate and ongoing pregnancy rate. Statistical analysis was performed by means of Student-t test and Fisher test. P<0,05 was considered statistically significant. Results were expressed as means ± SD.ResultsTabled 1ConclusionAccording to our results, the association of microdose GnRH analog desensitization, tamoxifen, metformin and low doses of gonadotrophins in patients who need IVF or ICSI, resulted in a novel approach to reduce significantly the ART cost without compromising the pregnancy outcome. ObjectiveTo evaluate the effectiveness of a low cost novel ovulation induction protocol for IVF/ICSI. To evaluate the effectiveness of a low cost novel ovulation induction protocol for IVF/ICSI. DesignProspective study. Prospective study. Materials and methodsForty non insuline resistant infertile patients underwent IVF/ICSI during August and September of 2004.Twenty out of forty patients received 40 μg of leuprolide acetate twice a day and 650 mg of metformin, starting the first day of the ART cycle until hCG administration. On day two the ovulation induction began with 60 mg of tamoxifen per day during four days associated with low doses of urinary gonadotrophin therapy (Group I). Twenty patients were assigned as the control group (Group II). They received leuprolide acetate 1 mg/day from the midluteal phase of the previous cycle in association with recombinant FSH (300 IU/day during the first four days of the treatment cycle) in a step down protocol. The variables analyzed included age, International Units (IU) of gonadotrophins, stimulation length, stimulation cost (U$S), number of oocytes retrieved,number of embryos transferred, implantation rate and ongoing pregnancy rate. Statistical analysis was performed by means of Student-t test and Fisher test. P<0,05 was considered statistically significant. Results were expressed as means ± SD. Forty non insuline resistant infertile patients underwent IVF/ICSI during August and September of 2004.Twenty out of forty patients received 40 μg of leuprolide acetate twice a day and 650 mg of metformin, starting the first day of the ART cycle until hCG administration. On day two the ovulation induction began with 60 mg of tamoxifen per day during four days associated with low doses of urinary gonadotrophin therapy (Group I). Twenty patients were assigned as the control group (Group II). They received leuprolide acetate 1 mg/day from the midluteal phase of the previous cycle in association with recombinant FSH (300 IU/day during the first four days of the treatment cycle) in a step down protocol. The variables analyzed included age, International Units (IU) of gonadotrophins, stimulation length, stimulation cost (U$S), number of oocytes retrieved,number of embryos transferred, implantation rate and ongoing pregnancy rate. Statistical analysis was performed by means of Student-t test and Fisher test. P<0,05 was considered statistically significant. Results were expressed as means ± SD. ResultsTabled 1 ConclusionAccording to our results, the association of microdose GnRH analog desensitization, tamoxifen, metformin and low doses of gonadotrophins in patients who need IVF or ICSI, resulted in a novel approach to reduce significantly the ART cost without compromising the pregnancy outcome. According to our results, the association of microdose GnRH analog desensitization, tamoxifen, metformin and low doses of gonadotrophins in patients who need IVF or ICSI, resulted in a novel approach to reduce significantly the ART cost without compromising the pregnancy outcome.

Comparação entre três esquemas de indução da ovulação para inseminação intra-uterina com relação à espessura endometrial e taxa de gravidez

PURPOSE: to compare pregnancy rates and mean endometrial thickness obtained with three protocols for induction of ovulation in cycles of intrauterine insemination (IUI). METHODS: one hundred and ten IUI cycles were retrospectively evaluated in the study, divided into three groups, according to the used ovulation induction protocols: 100 mg clomiphene citrate (CC) on days 3 to 7 of the cycle (CC group, n=24), 100 mg/day CC on days 3 to 7 of the cycle + 75 IU/day of human menopausal gonadotrophin (hMG) on days 3, 5 and 7 of the cycle (CC+hMG group, n=29), and 75 IU/day of hMG on days 3 to 8 of the cycle (hMG group, n=57). Statistical analysis was performed using Student's t test to compare the means and the c2 test to compare the rates. Results were considered statistically significant at p<0.05. RESULTS: the patients' average age at the onset of the first cycle was 2340 years (mean age, 33.3 years). There were no statistically significant differences between groups. The mean endometrial thickness on the day of the human chorionic gonadotrophin (hCG) administration was significantly higher in the hMG group (10.2±0.2 mm), as compared with the CC and CC+hMG group (7.9±0.4 and 8.7±0.2 mm, respectively, p<0.001). The overall clinical pregnancy rate was 18.2%, and there were no statistically significant differences between the groups (CC group=12.5%; CC+hMG group=24.1% and hMG group=19.3%). CONCLUSION: the results indicate higher mean endometrial thickness in the hMG group as compared with the CC group and the CC+hMG group. There were no significant differences between clinical pregnancy rates obtained with each protocol (CC, CC+hMG and hMG).

Relationship Between Maternal Age and Aneuploidy in in vitro Fertilization Pregnancy Loss

The goal of this retrospective study was to determine the rate of miscarriage in in vitro fertilization (IVF) pregnancies after sonographic confirmation of cardiac activity at 7 weeks gestation. The study included 2014 consecutive IVF pregnancies, from the years 1991 to 1996, in which fetal cardiac activity was documented. Standard ovulation induction protocols were used to prepare for IVF-embryo transfer. Selected embryos were transferred into the uterine cavity approximately 72 hours after being retrieved. The number of embryos transferred increased with advancing age, up to 5 for women more than 40 years of age. Pregnancy loss (spontaneous abortion [SAB]) occurred in 233 patients, 11.6% of the total. Losses clearly increased with advancing age, from 5.3% in women 30 years of age and younger to 22.2% in those aged 40 and older. Pregnancy loss was more likely in women with singleton pregnancies compared with those with multiple gestations (16.1% vs. 5.4%), but the former women were significantly older. More than one fourth of women aged 40 years and older failed to deliver a live-born infant. An age effect was also noted in women with SAB, but the SAB rate for multiple gestations was lower than in singleton pregnancies for all age groups. Cytogenetic analysis was carried out in 74 pregnancy losses and an abnormal karyotype was identified in 52 of them (71.2%). The rate of chromosomal aneuploidy was 82% in women aged 40 and older and 65% in those less than 40 years of age (odds ratio, 3.35). Approximately 4 in every 5 fetuses with an abnormal karyotype had trisomies, most frequently in chromosomes 21, 16, 22, 15, and 18 (in descending order). These data are from a single institution, and fetal age was precisely documented in all cases. A significant risk of pregnancy loss must be taken into account when counseling women about how many embryos will be transferred after IVF. Chromosomal aneuploidy appears to be the major underlying cause of these losses.

Comparison of Pregnancy Outcomes of Progesterone or Progesterone + Estradiol for Luteal Phase Support in ICSI-ET Cycles

Objective: To find out the effect of estradiol with progesterone for luteal phase support in IVF-ICSI cycles. Materials and Methods: Patients were accepted for treatment in the ART unit of Selcuk University, Meram Faculty of Medicine, between January 2001 and March 2003. The study was done in a prospective manner. The age range of 252 women was 19–41 years and the total number of cycles was 310. All patients were treated with a long ovulation induction protocol. Patients were treated and divided into two groups in a randomized manner: group I used only 600 mg/day divided into three equal doses of micronized progesterone vaginally, and group II used transdermal estradiol 100 µg/day + 600 mg/day vaginal micronized progesterone. Results: 310 ICSI cycles were carried out in 252 infertile couples between January 2001 and March 2003. From 22 of these cycles, oocytes were retrieved but no embryos were developed. In the remaining 288 cycles there were embryo transfers. All embryo development was achieved by ICSI treatment. In 148 out of 288 cycles, the luteal phase was supported only by vaginal micronized progesterone (group I). On the other hand, the remaining 140 cycles received vaginal micronized progesterone plus transdermal estradiol 100 µg/day (group II). The number of β-hCG-positive results in group I and group II were 20 (13.5 %) and 54 (38.5%) respectively. Conclusion: Adding estradiol to progesterone for luteal phase support in ICSI-ET cycles may increase implantation and pregnancy rates.

A prospective randomized study of three ovulation induction protocols for IVF: GnRH agonist versus antagonist with and without low dose hCG

The purpose of this study was to compare the effectiveness of three different protocols of ovulation induction (OI) for IVF. A prospective randomized study. 73 women under the age of 40 underwent OI. All patients were injected with an initial urinary human pure FSH= uhFSH (Fertinorm P) dosage ranging from 225–300IU daily, and grouped as follows:(group A: n=26) uhFSH after midluteal pituitary desensitization with Suprecure; (group B: n=24) Full doses of uhFSH were administered until follicles reached 14 mm, at which point the uhFSH dosage was decreased to 150IU and GnRH antagonist (Cetrorelix) 0.25 mg with 200 IU human chorionic gonadotropin (hCG) was begun; (group C: n=23) The same procedure until 14mm in follicular diameter as in group B and then more 75IU uhFSH dosage was increased and Cetrorelix 0.25mg was begun. At first we compared the number of retrieved oocytes, fertilization rate, D3 high-quality embryo rate, and the number of transferred embryos. Next, we investigated the pregnancy rate and the incidence of ovarian hyperstimulation syndrome (OHSS=defined as more than 50 mm in ovarian diameter). Although group B required significant lower gonadotropin injection than other protocols (2388±455, 1862±496, and 2159±517 IU in group A, B and C, respectively), it has shown the highest pregnancy rate of the three protocols (47.1%=8/17, 61.9%=13/21,and 42.1%=8/19 in group A, B and C, respectively). And group B (31.8%=7/22) resulted significantly lower OHSS rate than group A (70.0%=14/20, P<0.05), and had a tendency being lower than C (60.0%=12/20). Group A includes one severe OHSS case, which froze all embryos. Age (32.5±4.1, 34.4±3.7 33.0±3.5 year-old), number of retrieved oocytes (14.4±7.6, 10.5±6.7,11.9±5.1), fertilization rate (70.9, 77.9, 72.0%), D3 high-quality embryo rate (15.9, 30.3, 22.9 %), and number of transferred embryos (2.0±0.2, 2.0±0.5, 2.0±0.4) were not significantly different in group A, B and C, respectively. This study demonstrated that the protocol of GnRH antagonist with low-dose hCG is economical for patients because it requires lower amount of gonadotropin, and is also clinically beneficial because it keeps pregnancy rates high compared with the other two OI protocols. Moreover, this procedure reduces the risk of OHSS while allowing similar oocyte retrieval and embryo development in comparison to other methods.

Unbalanced sex ratio in newborns obtained by intrauterine inseminations

The intrauterine insemination (IUI) model represents an ideal technique to prove if the theory that Y-bearing spermatozoa swim faster but live less than X-bearing sperm. If true, a greater proportion of male newborns should be expected with IUI, since couples are requested to avoid intercourse during the fertile period until the insemination is performed around ovulation. The proportion of male to female newborns obtained by intrauterine insemination in our center was 3.4:1, and was not influenced by the sperm separation technique used, nor the ovulation induction protocol employed. This unbalanced sex ratio in favor of male newborns obtained by IUI requires further prospective studies with larger number of participants to be confirmed, but is certainly an information that needs to be discussed with the infertile couples prior to treatment.

A novel approach to ovulation induction (O.I.) in patients with repeated failed O.I. cycles

Patients who have done repeated O.I. Cycles and consistently yield negative results continue to be a challenge to Reproductive Endocrinologists. Numerous controlled ovarian stimulation protocols have been attempted in these patients with minimal success. The purpose of this study was to initiate a new ovulation induction protocol utilizing TID dosing versus the standard QD or BID dosing regimen to achieve a better stimulation and a higher pregnancy rate.

Bone resorption starts at 14 days of treatment with gonadotropin-releasing hormone agonist in in vitro fertilization cycles

The effect of gonadotropin-releasing hormone agonist (GnRH-a) use on bone turnover was investigated in a prospective cohort study of female patients undergoing in vitro fertilization (IVF) treatment. In 46 couples diagnosed with male-factor infertility, the women underwent a long step-down ovulation induction protocol. Urinary cross-linked N-telopeptide (uNTx) level was used to demonstrate bone turnover rate and was measured at the first day of GnRH-a administration, the first day of gonadotropin administration, the day after human chorionic gonadotropin injection and 12 days after embryo transfer. Urinary NTx levels (mean ± standard deviation (SD)) were 71 ± 34, 81 ± 40, 81 ± 50 and 83 ± 47 nmol BCE/mmol creatinine (BCE, bone collagen equivalents), respectively. There was no statistically significant difference between the four measurements (p = 0.28). In 19 women GnRH-a was administered for ⩾ 14 days. Urinary NTx values of this group and the remaining 27 patients after GnRH-a treatment were 96.2 ± 40.7 and 71.5 ± 36.8 nmol BCE/mmol creatinine (mean ± SD), respectively. The difference between these groups was statistically significant (p = 0.038). These findings suggest that < 14 days' use of GnRH agonist in IVF patients has no effect on bone metabolism. To our knowledge, this is the first study demonstrating that the effect of agonists on bone metabolism starts as soon as estradiol suppression has started.

A novel protocol of ovulation induction with delayed gonadotropin-releasing hormone antagonist administration combined with high-dose recombinant follicle-stimulating hormone and clomiphene citrate for poor responders and women over 35 years

Objective To evaluate the efficacy of a novel protocol of ovulation induction for poor responders. Design Prospective, controlled, clinical study. Setting Research institute's reproductive unit. Patient(s) One hundred forty-five infertile women, aged 27–39 years, candidates for assisted reproductive techniques (ART). Intervention(s) Before undergoing ART, 85 patients received clomiphene citrate, high-dose recombinant human FSH, and a delayed, multidose GnRH antagonist, whereas 60 patients underwent a standard long protocol. Main outcome measure(s) Estradiol levels (pg/mL), cancellation rate, oocyte retrieval, embryo score, and fertilization and pregnancy rates. Result(s) Patients undergoing the study protocol obtained lower cancellation rates (4.7% vs. 34%) and higher E 2 levels (945.88 ± 173.2 pg/mL vs. 169.55 ± 45.07 pg/mL), oocyte retrieval (5.56 ± 1.13 vs. 3.36 ± 1.3), and pregnancy (22.2% vs. 15.3%) and implantation rates (13.5% vs. 7.6%) compared with those receiving the long protocol. Age negatively correlated with ovarian response in the latter, whereas the ovarian outcome results were comparable in younger (<35 yrs) and older (>35 yrs) women treated with the study protocol. Conclusion(s) The proposed protocol of ovulation induction can be usefully administered in poor responders as well as in aged woman, probably because the delayed administration of GnRH antagonist prevents its adverse effects on ovarian paracrine activity and on oocyte maturation.

Effects of ovulation induction on ovarian morphology: an animal study.

The aim of this study was to investigate whether the ovulation induction has relation with postneoplastic lesions. Seventy-eight female, 90-day-old rats were enrolled for the trial. They were divided into three groups. In the first group, 13 rats received one cycle of ovulation induction with Follitropin Beta and human chorionic gonadotropin. The second group of 13 rats received three cycles of ovulation induction, and the third study group consisted of 13 rats which received six cycles of ovulation induction. Each group had a control group consisting of same number of rats that had not received ovulation induction. At the 12th month after the ovulation induction protocols ended, rat ovaries were extirpated for histopathological examination. In histopathological examination, malignant lesions, ovarian cyst and cyst diameter, epithelial stratification, epithelial tufting, mitotic index, polymorphism of epithelial cells and nucleus, epithelial cell nuclear diameter, chromatin density nuclear atypia, and mitotic activity in ovarian cyst epithelium were evaluated. No malignant ovarian lesion was found in the three groups. Ovarian cyst development was most frequent in the rats that underwent six cycles of ovulation induction. Epithelial stratification and tufting were most frequent in the rats which underwent ovulation induction six times. Significant difference was found between induction and control groups in second and third groups for cellular and nuclear polymorphism, presence of nucleolus, and nuclear chromatin density. Although development of malignant lesion were not found in any of the rat ovaries after ovulation induction, increase in the prevalence of epithelial dysplasia especially with increase in the number of induction cycles shows that some ovarian pathologies can occur subsequent to ovulation induction.

Effects of ovulation induction on ovarian morphology: an animal study

ObjectiveThe aim of this study was to investigate whether the ovulation induction has relation with postneoplastic lesions.Materials and methodsSeventy-eight female, 90-day-old rats were enrolled for the trial. They were divided into three groups. In the first group, 13 rats received one cycle of ovulation induction with Follitropin Beta and human chorionic gonadotropin. The second group of 13 rats received three cycles of ovulation induction, and the third study group consisted of 13 rats which received six cycles of ovulation induction. Each group had a control group consisting of same number of rats that had not received ovulation induction. At the 12th month after the ovulation induction protocols ended, rat ovaries were extirpated for histopathological examination. In histopathological examination, malignant lesions, ovarian cyst and cyst diameter, epithelial stratification, epithelial tufting, mitotic index, polymorphism of epithelial cells and nucleus, epithelial cell nuclear diameter, chromatin density nuclear atypia, and mitotic activity in ovarian cyst epithelium were evaluated.ResultsNo malignant ovarian lesion was found in the three groups. Ovarian cyst development was most frequent in the rats that underwent six cycles of ovulation induction. Epithelial stratification and tufting were most frequent in the rats which underwent ovulation induction six times. Significant difference was found between induction and control groups in second and third groups for cellular and nuclear polymorphism, presence of nucleolus, and nuclear chromatin density.ConclusionsAlthough development of malignant lesion were not found in any of the rat ovaries after ovulation induction, increase in the prevalence of epithelial dysplasia especially with increase in the number of induction cycles shows that some ovarian pathologies can occur subsequent to ovulation induction.

Alternative approaches in the management of poor response in controlled ovarian hyperstimulation (COH).

Improving pregnancy rates in patients with many failed attempts remains a challenge during IVF-ET or ICSI-ET programs. The availability of good-quality oocytes is a prerequisite for good results in such programs. The use of a personalized protocol for controlled ovarian hyperstimulation (COH) that gives the best possible results for the specific patient is a main factor for the success in IVF or ICSI. The response of many patients to the ovarian stimulation used is very poor, giving fewer oocytes than expected, resulting in much lower, if any, pregnancy rates. The definition of a poor responder is not clear and differs among researchers. A variety of strategies have been used to improve response in these patients, regardless of the definition used. These include various ovulation induction protocols that we believe might assist these patients achieve a pregnancy. The difficulty is greater due to the fact that poor responders are not a homogeneous group and each patient may have a different cause. More studies with large numbers of patients are needed in order to find those protocols that could provide these couples with an acceptable pregnancy rate.

Improved monofollicular ovulation in anovulatory or oligo-ovulatory women following a low dose step-up protocol with weekly increments of 25 IU follitropin beta

Objective To assess the efficacy and efficiency of two low-dose step-up protocols for ovulation induction in women with anovulatory infertility (WHO group II) using follitropin beta delivered via Pen device allowing dose adjustments as low as 25 IU. Design Randomized, prospective, multicentre (n = 18) clinical trial. Material and Methods Anovulatory or oligo-ovulatory women between 18 and 39 years of age with a body mass index between 18 and 33 kg/m2 were randomized to two treatment groups with weekly increments of 50 IU or 25 IU of follitropin beta (Puregon Pen®) after a starting dose of 50 IU for seven days. The dose increments were only allowed when no follicles ≥ 12 mm were seen on ultrasound. Treatment with Puregon Pen® was continued until one follicle ≥ 18 mm was present. Ovulation was then triggered with hCG (10 000 IU). The cycle was cancelled, when more than three follicles ≥ 15 mm were present. Results In total, 158 women were treated. Eighty women were randomized to the 25 IU increment group compared to 78 in the 50 IU increment group. There were no major differences in the demographic and infertility characteristics. The ovulation rate was 81.3% in the 25 IU and 60.3% in the 50 IU groups, respectively (p = 0.009). Of all treated women, 41.3% and 21.8% in the 25 and 50 IU groups, respectively, had monofollicular growth (only one follicle ≥ 16 mm and no other follicles ≥ 12 mm, p = 0.010). The total dose of recombinant FSH used was lower in the 25 IU group (887 IU versus 984 IU, p = 0.013). There was no significant difference in treatment duration (14.0 and 13.4 days in the 25 IU and 50 IU increment groups, respectively). More cancellations due to high ovarian response were seen in the 50 IU group (n = 16, 20.5%) compared to the 25 IU group (n = 4, 5.0%, p = 0.004). Ongoing pregnancy rate per started cycle was 20.0% in the 25 IU group and 12.8% in the 50 IU group (not significant). There were two multiple pregnancies, both in women treated with 25 IU increments. Two women, one in each group, were hospitalized because of ovarian hyperstimulation syndrome. Conclusions: A low-dose step-up protocol with a starting dose of 50 IU follitropin beta and 25 IU weekly increments using Puregon Pen(r) produces a more controlled ovarian stimulation ideally suited for ovulation induction. This 25 IU increment regimen is more effective and efficient than 50 IU increments, as shown by an increased monofollicular growth, higher ovulation rate and a lower total dose of follitropin beta used. Supported by: NV Organon, Oss, The Netherlands.

Estimation of second polar body retention rate after conventional insemination and intracytoplasmic sperm injection: in vitro observations from more than 5000 human oocytes.

Tripronucleate (3pn) development after conventional insemination (CONV) or ICSI was analyzed to estimate the rate of second polar body retention giving rise to 3pn formation. Data from 453 consecutive IVF cycles were reviewed during a 6-month period. Mature oocytes were monitored in ICSI (n = 3195) and CONV (n = 2274) groups by fertilization assessment 16-18 h post-insemination. Ovulation induction protocols and in vitro culture conditions remained constant during the study interval. Normal (2pn) fertilization occurred in 74.2% and 70.5% for CONV and ICSI groups, respectively (p < 0.003). 1pn formation was observed in 4.5% of CONV oocytes, and 2.5% of ICSI oocytes (p < 0.001); 3pn formation was 8.1% in the CONV group, and 2.5% in the ICSI group (p < 0.0001). We observed 4pn formation in 0.4% of oocytes in the CONV group, but in only 0.04% of oocytes fertilized with ICSI (p < 0.007). Cellular degeneration occurred in 2.4% of oocytes inseminated conventionally, and in 3.5% of oocytes fertilized by ICSI (p = 0.02). Maternal age did not impact pronuclear status. We found the 3pn formation rate after ICSI to be approximately one-third that observed in the CONV group. Extrapolating the ICSI data to the CONV data, it may be inferred that 2.5% of 3pn development after CONV was due to second polar body retention. This suggests that 5.6% of CONV oocytes showed dispermic fertilization. Decreasing oocyte quality with increasing maternal age had no apparent influence on any of the fertilization outcomes.

Is there a future for ovulation induction in the current era of assisted reproduction?

The clinical use of medical induction of ovulation in normogonadotrophic anovulatory women (WHO II), including polycystic ovary syndrome, is increasingly questioned. However, we believe that this treatment modality still represents a highly effective means of fertility treatment in women with low pregnancy chances without intervention. A conventional treatment algorithm involving clomiphene citrate (CC) followed by FSH induction of ovulation may result in a 71% cumulative singleton live birth rate. In attempts to improve treatment outcome further and reduce complication rates, new compounds such as insulin-sensitizing agents or aromatase inhibitors are currently used increasingly. Approaches such as patient selection for different treatment modalities on the basis of initial screening characteristics and alternative protocols for FSH ovulation induction may also be proposed to render treatment algorithms more patient tailored and therefore improve overall outcomes. More research is needed in this area, rather than referring these patients to assisted reproduction prematurely. This may lead to a more individually tailored approach for ovulation induction in a given patient, resulting in a further improvement of the balance between chances for success versus complications.

Ovarian wedge resection by minilaparatomy in infertile patients with polycystic ovarian syndrome: a new technique

Objective: To determine the effects of ovarian wedge resection by minilaparotomy in infertile patients with polycystic ovarian syndrome (PCOS). Study design: One hundred and thirty-four anovulatory patients with PCOS, who were previously treated with clomiphene citrate and gonadotropins and did not concieve were operated via minilaparotomy with microsurgical principles and ovarian wedge resection was performed on each subject. Pregnancy rates and adhesion formation were investigated retrospectively. Results: A total of 121 pregnancies were achieved in 2 years (90%). One hundred and four patients concieved within the first 6 months (78%) and the remaining 17 patients concieved within 2 years (13%) following the operation. Sixty-eight patients had a second pregnancy later. In the post-operative period, 24 patients had cesarean delivery and 20 had diagnostic laparoscopy. Out of these 44 patients, only 5 of them were found to have minimal adhesions. Conclusion: This technique offers high pregnancy rates and minimal adhesion formation. Ovarian wedge resection by minilaparotomy might be an alternative treatment approach in patients with PCOS who did not concieve with standart ovulation induction protocols.

Significance of maternal and paternal age in assisted reproduction programs

Many infertile couples try to become parents spontaneously, neglecting the possibility to conceive artificially, so they seek medical help in their late reproductive age. Major aspects of maternal age in regard to assisted reproduction consider oocytes, ovaries and endometrium. Also, some habits and maternal diseases associated with aging may have an impact on fertility (smoking, atherosclerosis, previous gynecological operations etc.). Even though estimating the ovarian reserve is the most objective test in assessing female fertility, it has a limited predictive value in younger women. A short protocol of ovulation induction showed best results in women with poor ovarian reserve, but recent studies recommend low-dose gonadotropin-releasing hormone agonists in these cases. With aging, sperm parameters become worse, which points to the neglected role of the father in assisted reproduction. Thus, parental age plays an important role in assisted reproductive programs.

Controlled ovarian stimulation and ultrasound guided follicular aspiration in the baboon (Papio cynocephalus anubis).

The objective of this study was to investigate whether baboon females respond to an ovarian stimulation protocol incorporating pituitary suppression with a GnRH agonist (GnRHa) and highly purified human FSH (hphFSH) with follicular development and oocyte maturation. An ovulation induction protocol was applied to 5 adult female baboons with a history of regular menstrual cycles (33-34 days). A long-acting GnRHa implant containing goserelin acetate was placed s.c. on days 22-24 of their menstrual cycle. Daily hphFSH (75 IU im) treatments were started approximately 10 days following menses. When the majority of the follicles were > or = 5 mm in diameter and the E2 levels had reached a maximum, hCG (2000 IU i.m.) was administered to induce final maturation of the oocytes and ovulation. 30 to 34 h after hCG administration, transabdominal follicular aspiration was performed using a variable frequency transvaginal transducer with ultrasound. A total of 71 oocytes were collected (average: 17). 91% of the oocytes were morphologically normal indicating that they were appropriate for in vitro insemination.

Ovarian stimulation and ultrasound-guided oocyte retrieval in baboon (Papio Cynocephalus Anubis) during pituitary suppression with a GnRH agonist.

The objective of this study was to investigate whether baboon females respond to an ovarian stimulation protocol incorporating pituitary suppression with a GnRH agonist (GnRHa) and either highly purified human FSH (hphFSH) or recombinant human FSH (rhFSH) with follicular development and oocyte maturation. A modified human ovulation induction protocol was applied to 5 adult female baboons with a history of regular menstrual cycles (33-34 days). A long-acting GnRHa implant containing goserelin acetate was placed subcutaneously (s.c.) on Days 22-24 of their menstrual cycle. Concentrations of serum oestradiol (E2), progesterone (P4) and human FSH were obtained by ELISA. Menses occurred approximately 10 days after GnRHa implantation. Daily hphFSH or rhFSH (75 IU i.m.) treatments were started approximately 10 days following menses. When the majority of follicles were > or = 5 mm in diameter and the E2 levels had reached a maximum, hCG (2000 IU i.m.) was administered to induce final maturation of oocytes and ovulation. Thirty to 34 h after hCG administration, transabdominal follicular aspiration was performed using a variable frequency transvaginal transducer with ultrasound. A total of 71 oocytes were collected from 4 animals (average: 17). The meiotic maturity of oocytes was evaluated 3 h after retrieval. Ninety-one percent of oocytes were in metaphase 2 and of grades I and II which are appropriate for in vitro insemination.