Adding human menopausal gonadotrophin to antagonist protocols – is there a benefit?

The objective of this retrospective analysis was to compare the clinical outcomes of recombinant FSH (r-FSH) with combination r-FSH plus human menopausal gonadotrophin (HMG) protocols in a large private practice using a single IVF laboratory, from 2001 to 2003. Patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) antagonist protocol using r-FSH or combination r-FSH plus HMG. When two or more follicles had attained a minimum mean diameter of 20 mm, follicular triggering was achieved with either recombinant HCG (r-HCG; Ovidrel, 250 microg s.c.) or urinary HCG (u-HCG; 10,000 IU i.m.). The main outcome measures were number of oocytes retrieved and clinical pregnancy rate. There was a lower percentage of cancelled cycles and an increased number of oocytes retrieved, mature oocytes, oocytes that fertilized, embryo that cleaved and a tendency towards higher clinical pregnancy rates in patients treated with r-FSH alone compared with those treated with r-FSH plus HMG. Patients treated with r-FSH plus HMG had lower miscarriage rates and the live birth rate was similar in both treatment groups. In conclusion, irrespective of age, using a treatment regimen consisting of a combination of HMG plus r-FSH was not beneficial compared with r-FSH alone in patients using a GnRH antagonist protocol.     

Recombinant HCG for triggering ovulation increases the rate of mature oocytes in women treated for ICSI

Purpose

To conduct a prospective randomized study in order to investigate the effect of recombinant HCG (rHCG) on oocyte nuclear and cytoplasm maturity compared to urinary HCG (uHCG), for inducing ovulation in women treated with ICSI for male factor infertility.

Materials and Methods

We compared 89 patients randomly assigned to one of the two study groups. Group A consisted of 42 women who received a subcutaneous (s.c.) injection of 250 μg rHCG and group B consisted of 47 patients receiving an intramuscular (i.m.) injection of 10,000 IU uHCG.

Results

Patients treated with rHCG showed a rate of metaphase II oocytes, a number of metaphase II oocytes with mature cytoplasm and a rate of metaphase II oocytes with mature cytoplasm calculated from total MII oocytes statistically higher than in patients treated with uHCG. However this differences were not associated with a significantly better clinical outcome.

Conclusion

Our data show that in women treated with ICSI for male factor infertility, rHCG increases the rate of metaphase II oocytes, the number and the rate of MII oocytes with mature cytoplasm compared to uHCG. A larger study comparing transfer cycles of embryos all derived from oocytes with mature cytoplasm and transfer cycles of embryos all derived from oocytes with immature cytoplasm may be needed to clarify clinical correlations.     

Pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin in healthy male and female volunteers

The pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin (rHCG) were investigated in three studies of healthy volunteers. After single intravenous doses of 25, 250 and 1000 microg, rHCG and urinary HCG (uHCG) showed linear pharmacokinetics described by a bi-exponential model, although the area under the curve (AUC) for uHCG was ~29% lower than for rHCG. After intramuscular or subcutaneous administration (absolute bioavailability, 40-50% for both), rHCG pharmacokinetics could be described by a first-order absorption, one-compartment model. During multiple subcutaneous dosing, the amount of HCG increased by approximately1.7-fold. A comparison of liquid and freeze-dried rHCG and freeze-dried uHCG showed pharmacokinetic bioequivalence. In down-regulated male subjects, single doses of 125 microg rHCG, given intravenously, intramuscularly or subcutaneously, produced comparable increases in serum testosterone, inhibin and 17beta-oestradiol, with little further increase during repeated subcutaneous administration (in female subjects, this produced a sustained comparable increase in serum androstenedione and testosterone concentrations). In conclusion, the pharmacokinetics and pharmacodynamics of rHCG are similar to those of uHCG and are not affected by the use of different formulations. In healthy subjects, rHCG produces pharmacodynamic responses consistent with HCG physiology and is suitable for use in the same clinical indications as uHCG. The secured source and high purity of rHCG may offer important advantages.     

Precycle administration of GnRH antagonist and microdose HCG decreases clinical pregnancy rates without affecting embryo quality and blastulation

The outcome of a novel protocol utilizing precycle gonadotrophin-releasing hormone (GnRH) antagonist administration and LH activity support with microdose recombinant human chorionic gonadotrophin (HCG) was compared to GnRH agonist long protocol used in patients undergoing their first ICSI (n=707) or IVF (n=571) cycles, which had resulted in one or two blastocyst transfers. In GnRH antagonist cycles, cetrorelix acetate (3 mg) was administered s.c. 4 days before FSH stimulation and a repeat dose was given when the lead follicular diameter was 13-14 mm. LH support was provided by recombinant HCG (2.5 microg). Embryo progression and blastulation were evaluated using embryo progression indices and blastocyst quality scores. The tested protocol demonstrated reduced implantation and clinical pregnancy rates as compared with GnRH agonist long protocol, although the embryo progression and blastulation parameters and blastocyst quality were comparable among the groups. Logistic regression models further supported the significant negative impact of GnRH antagonist/microdose HCG protocol on clinical pregnancy rates in both ICSI and IVF patients. Assisted reproduction cycles with fresh blastocyst transfers utilizing precycle GnRH antagonist administration and microdose HCG support resulted in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles, although the embryo progression and blastulation parameters were comparable.     

GnRH agonist versus recombinant HCG in an oocyte donation programme: a randomized,prospective, controlled,assessor-blind study

The use of gonadotrophin-releasing hormone (GnRH) agonists for triggering ovulation remains controversial. The primary objective of this study was to evaluate the incidence of ovarian hyperstimulation syndrome (OHSS) following GnRH agonist versus recombinant human chorionic gonadotrophin (HCG) as methods for triggering ovulation. A second aim was to compare the clinical outcome and embryo quality according to the two procedures. The cycle characteristics of 100 oocyte donors undergoing ovarian stimulation and IVF outcomes of their 100 oocyte recipients were analysed. Donors were prospectively randomized into two groups on the last day of ovarian stimulation: Group I received a single bolus of 0.2 mg of triptorelin and Group II received 250 μg of recombinant HCG. No differences were observed in the number of oocytes retrieved or in the proportion of metaphase II oocytes between the groups. The OHSS rate was higher in donors that received recombinant HCG (P = 0.003). Moreover, there was no significant difference between IVF parameters and outcome in the two groups. In conclusion, a GnRH agonist effectively triggers the final oocyte maturation in oocyte donors without negatively affecting implantation, pregnancy or miscarriage rates. Moreover, this regime effectively eliminates the risk of OHSS in this group of women.     

Impact of high basal FSH/LH ratio in women with normal FSH levels on in vitro fertilization outcomes

Abstract

Basal luteinizing hormone (LH) levels have also been suggested to impact on ovarian responsiveness as well as basal follicular stimulating hormone (FSH) levels. The aim of this study was to compare the in vitro fertilization (IVF) outcomes according to cycle day 3 FSH/LH ratio and to assess the proper stimulation protocol between gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist protocols. The retrospective cohort study recruited a total of 1211 women having the laboratory values of FSH (<10?IU/L) and LH within 3 months before IVF. Patients were treated with GnRH agonist long or GnRH antagonist protocols and stimulated with recombinant FSH (rFSH). The number of total retrieved oocytes and mature oocytes, implantation rate, clinical pregnancy rate and ongoing pregnancy rate were analyzed between groups: Group I: FSH/LH?<?2 and Group II: FSH/LH?≥?2. The Group II had the small number of retrieved oocytes and mature oocytes compared to the Group I (p?=?0.000). Clinical and ongoing pregnancy rate were lower in Group II (p?=?0.006, 0.006, respectively). In comparison of each protocol within groups, Group II showed significantly low pregnancy rate when GnRH antagonist was administered. In women with normal FSH level, high day 3 FSH/LH ratio can present subclinically low ovarian reserve and be predictive of lower pregnancy outcomes in fresh IVF cycles, and the choice of GnRH agonist can be related to favorable IVF outcomes.     

Optimal reproductive competence of oocytes retrieved through follicular flushing in minimal stimulation IVF

The objective of this study was to assess the reproductive competence of oocytes obtained by follicular flushing in poor responder patients. This prospective comparative study, at the University of Paris XI, Assistance Publique des Hopitaux de Paris, INSERM Unit 782, was performed on 165 infertile IVF embryo transfer candidates. A total of 271 consecutive minimal stimulation IVF cycles were studied. Oocyte retrieval was performed 34 h after human chorionic gonadotrophin administration and oocytes were allocated into two groups according to their retrieval method: oocytes obtained in the first follicular aspiration (FA, n = 127); and oocytes retrieved in the subsequent follicular flushing (FF, n = 102). The principal outcome was to evaluate clinical pregnancy and embryo implantation rates. Thus, patient characteristics, fertilization rate and clinical pregnancy rate per oocyte were comparable in both of groups. In contrast, embryo morphology (41 versus 59%, P < 0.01) and implantation rates (20.4 versus 34.8%, P < 0.04) were better in the FF group. In conclusion, an optimal reproductive competence was observed in oocytes retrieved by follicular flushing in minimal stimulation IVF in poor responder patients.     

Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate

Using data from a large prospective randomized controlled trial that evaluated the effect of recombinant LH (rLH)co-administration for ovarian stimulation, the present study assessed whether progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration was associated with pregnancy outcome. Progesterone concentration was measured on stimulation day 1 and on the day of HCG administration in 475 patients who underwent IVF/intracytoplasmic sperm injection treatment following ovarian stimulation with gonadotrophin-releasing hormone (GnRH) agonist and recombinant FSH with or without rLH administration from day 6 of stimulation. There was no significant association between the late-follicular-phase progesterone concentration and the clinical pregnancy rate. However, progesterone concentration was strongly associated with the number of follicles and retrieved oocytes. Late-follicular-phase LH concentration also showed a significant positive association with progesterone concentration (P = 0.018). Administration of rLH during ovarian stimulation did not affect progesterone concentration. The present study does not support an association between progesterone concentration on the day of HCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH agonists and gonadotrophins for assisted reproduction treatment.Instead, late-follicular-phase progesterone concentration appears to be governed by the number of preovulatory follicles and LH concentration.     

GnRH antagonists in ovarian stimulation for ICSI with oocyte restriction: a matched, controlled study

Italian legislation regarding reproductive medicine limits the number of embryos transferred per attempt to three. Thus, in order to achieve pregnancy, more IVF cycles may be required, generating a need for methods of ovarian stimulation with fewer side effects. The gonadotrophin-releasing hormone (GnRH) antagonists have several advantages in this respect, but there is a debate regarding a possible lower pregnancy rate from resulting cycles. This study evaluated the clinical applicability of GnRH antagonists for ovarian stimulation in young women undergoing intracytoplasmic sperm injection (ICSI) in which only three oocytes can be fertilized. The 200 women treated with GnRH antagonist had a significantly shorter stimulation and lower gonadotrophin consumption, oestradiol concentration, total and mature oocyte recovery as compared with 200 matched controls treated with GnRH agonist. No differences were found between the groups in the number of normal zygotes, total cleaved, transferred and high quality embryos, or in the clinical outcomes. Thus, the previously reported lower pregnancy rate in GnRH antagonist cycles may be related to the oocyte characteristics. Finally, under conditions of oocyte number restriction, the GnRH antagonist-based cycles may be proposed as an efficacious, safe and minimally invasive alternative to GnRH agonist in a standard long protocol.     

Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study

This randomized controlled study compared the effectiveness of a gonadotrophin releasing hormone (GnRH) antagonist protocol with or without oral contraceptive (OC) pretreatment on the number of oocytes retrieved in IVF or intracytoplasmic sperm injection (ICSI) patients. Sixty-four patients were randomized to start recombinant human FSH (r-hFSH) on day 2 or 3 after OC withdrawal (OC group) or on day 2 of a natural cycle (control group). From stimulation day 6 onwards, all patients were treated with daily (0.5 mg/ml) GnRH antagonist (Antide). OC pretreatment resulted in significantly lower starting concentrations of FSH, LH and oestradiol (P < 0.001) and a thinner endometrium (P < 0.0001). In the early stimulation period, fewer large follicles were found after OC pretreatment, leading to a significantly extended stimulation period (11.6 versus 8.7 days, P < 0.0001) with more follicles on the day of recombinant human chorionic gonadotrophin administration (15.4 versus 12.5, P = 0.02) and more oocytes retrieved (13.5 versus 10.2, P < 0.001) as compared with the control group. GnRH antagonist regimen, pretreated with OC, prevented the early endogenous FSH rise and improved follicular homogeneity, resulting in more oocytes. As a consequence of the extended treatment period, more rhFSH was required.     

Comparison of short and long ovulation induction protocols used in ART applications according to the ovarian response and outcome of pregnancy

This retrospective study was designed to determine whether there is any difference between short and long protocol ovulation induction with Gonadotropin Releasing Hormone agonist (GnRHa) and gonadotropins used in Assisted Reproductive Technology (ART) applications according to the number of retrieved oocytes, oocyte maturity, fertilization rates, embryo quality and the outcome of pregnancies. 240 cycles consisting of in vitro fertilization (IVF) cycles without andrologic factor and intracytoplasmic sperm injection (ICSI) cycles were evaluated. 112 cycles which were induced by short protocol GnRHa and Follicle Stimulating Hormone (FSH) + Human Menopausal Gonadotropin (HMG) combinations and 128 cycles which were induced by long protocol GnRHa and FSH + HMG combinations were compared according to the number of retrieved oocytes, cancellation rate of cycles, oocyte maturity, fertilization rates, embryo quality and pregnancy rates. The cancellation rate for short protocol cycles were found to be significantly higher than those with long protocol. The number of retrieved oocytes, mature oocytes and fertilized oocytes were also found significantly lower. The quality of embryos did not show any significant difference between these groups. The clinical pregnancy rates were evidently found to be high in the long protocol cycles. As a conclusion we have found that while the number of retrieved oocytes, mature oocytes, fertilized oocytes and clinical pregnancy rates were increasing, the cancellation rate of cycles were decreasing significantly in ART cycles induced by long protocol. Received: 26 October 2000 / Accepted: 23 January 2001     

Comparison of different stimulation protocols efficacy in poor responders undergoing IVF: A retrospective study

Purpose: To compare the efficacy of different stimulation protocols on pregnancy outcomes in poor responders undergoing in vitro fertilization (IVF). Materials and methods: This was a retrospective study to compare the efficacy of four different protocols including gonadotropin-releasing hormone (GnRH) agonist (long, short and miniflare) and GnRH antagonist on pregnancy outcomes in poor responders. This investigation was performed on 566 poor respond patients who were candidates for IVF. Main outcome measures included the total number of oocytes and mature oocytes retrieved, pregnancy rates, implantation and overall cancellation rates which were compared between four mentioned groups. Results: Number of follicles >18?mm on hCG day were significantly higher in GnRH-a long versus GnRH antagonist, GnRH-a short and GnRH-a miniflare protocols. The mean number of oocytes and mature oocytes retrieved were significantly higher in GnRH-a long versus miniflare (4.7?±?3.05 versus 3.26?±?2.9 and 3.69?±?3.1 versus 2.65?±?2.2, respectively). There were no significant differences in implantation, pregnancy and overall cancellation rates between four groups. Conclusion: The present study suggests that the application of four different protocols in poor respond patients seem to have similar efficacy in improving clinical outcomes such as implantation, pregnancy rates and cancellation rate even though GnRH-a long protocol yielded more retrieved oocytes and mature oocytes compared to GnRH-a miniflare protocol.     

Impact of metformin therapy on ovarian stimulation and outcome in 'coasted' patients with polycystic ovary syndrome undergoing in-vitro fertilization

This study was designed to determine if metformin therapy improves ovarian stimulation and IVF outcomes in coasted patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). A retrospective data analysis was performed on women with clomiphene citrate-resistant PCOS treated with or without metformin, who underwent 72 cycles of IVF-embryo transfer with intracytoplasmic sperm injection (ICSI). In 59 cycles, patients were coasted to allow oestradiol concentrations to drop before human chorionic gonadotrophin administration. In patients undergoing coasting, the outcome of IVF with ICSI was compared in those who were treated and untreated. In patients treated with metformin, follicular fluid concentrations of testosterone and insulin were significantly lower (60.5 +/- 5 versus 79.1 +/- 6 ng/dl; P < 0.05 and 18 +/- 2.5 versus 22 +/- 2.4 micro IU/ml; P < 0.05 respectively), and the mean number of oocytes retrieved (22.3 +/- 2.4 versus 19.7 +/- 1.6) did not differ. The metformin-treated group showed an increase in the mean number of mature oocytes, oocytes fertilized and cleaving embryos (4-cell or greater by 72 h). However, in the group of patients undergoing coasting, maximum oestradiol concentrations and number of days of coasting were all lower in the metformin-treated group with increased clinical pregnancy rates (71 versus 30%, P < 0.05). Therefore, metformin use appears beneficial in improving IVF outcomes in clomiphene citrate-resistant PCOS patients.     

GnRH agonist versus GnRH antagonist in poor ovarian responders: a meta-analysis

The aim of this meta-analysis was to compare the efficacy of gonadotrophin antagonist (GnRH-ant) versus GnRH agonist (GnRHa) as coadjuvant therapy for ovarian stimulation in poor ovarian responders in IVF/intracytoplasmic sperm injection cycles. Search strategies included on-line surveys of databases such as MEDLINE , EMBASE and others. A fixed effects model was used for odds ratio (OR) and effect size (weighted mean difference, WMD). Six trials fulfilled the inclusion criteria (randomized controlled trials). There was no difference between GnRH-ant and GnRHa (long and flare-up protocols) with respect to cycle cancellation rate, number of mature oocytes and clinical pregnancy rate per cycle initiated, per oocyte retrieval and per embryo transfer. When the meta-analysis was applied to the two trials that had used GnRH-ant versus long protocols of GnRHa, a significantly higher number of retrieved oocytes was observed in the GnRH-ant protocols [P=0.018; WMD: 1.12 (0.18, 2.05)]. However, when the meta-analysis was applied to the four trials that had used GnRH-ant versus flare-up protocols, a significantly higher number of retrieved oocytes (P=0.032; WMD: -0.51, 95% CI -0.99, -0.04) was observed in the GnRHa protocols. Nevertheless, additional randomized controlled trials with better planning are needed to confirm these results.     

Randomized controlled pilot trial of luteal phase recombinant FSH stimulation in poor responders

This study investigated whether luteal phase initiation of FSH supplementation would improve oocyte yield compared with follicular phase administration in women with poor ovarian response (POR). A two-arm, randomized, open-label pilot trial was performed at a university-based infertility centre. In nine of 18 infertile women with a history of POR in a previous cycle [<5 follicles on day of human chorionic gonadotrophin (HCG) administration; <5 oocytes retrieved; previous IVF cycle cancellation due to POR] FSH was administered during the mid-luteal phase of the preceding menstrual cycle. The primary outcome measure was the number of oocytes retrieved. Secondary endpoints included: follicles >10 mm and >16 mm and oestradiol concentration on the day of HCG administration, peak oestrogen concentration, pregnancy and live birth rates. All endpoints comparing luteal versus follicular stimulation were similar. In paired analysis of patients in the luteal arm compared with the prior cycle, there was a significant increase in days of stimulation (P = 0.01) and number of follicles >10 mm (P = 0.02) and >16 mm (P = 0.02) on day of HCG administration. IVF outcomes with luteal phase FSH compared with follicular phase FSH were similar. Luteal phase initiation of FSH is a safe and potential alternative protocol in poor responders.     

Gonadotropin-releasing hormone agonist use in assisted reproduction cycles: the influence of long and short regimens on pregnancy rates.

OBJECTIVE: To compare the efficacy of GnRH agonists used in either the flare (short) or down-regulation (long) regimen as part of IVF or GIFT treatment cycles. DESIGN: Observational study. SETTING: Three IVF clinics. PATIENT(S): One thousand two hundred forty-four couples accepted for IVF or GIFT treatment at participating clinics. INTERVENTION(S): In vitro fertilization or GIFT protocols standard to each clinic were recorded. MAIN OUTCOME MEASURE(S): Treatment cycle characteristics and outcomes, including E2 level, number of oocytes retrieved, and clinical pregnancy rate. RESULT(S): At site 1, there were 146 clinical pregnancies in 980 flare cycles, for a pregnancy rate of 14.9%, compared with 148 clinical pregnancies in 650 down-regulation cycles, for a pregnancy rate of 22.8%. This difference persisted after adjustment for age, primary infertility diagnosis, GIFT or IVF therapy, and year of treatment, and appeared to be mediated largely by the number of oocytes retrieved (mean, 9.8 for downregulation and 8.7 for flare in the first cycle). Despite having fewer oocytes retrieved, women who received flare regimens had higher E2 levels before hCG administration. CONCLUSION(S): Women who received GnRH agonists in a flare regimen had 11% fewer oocytes retrieved and a 35% reduction in the clinical pregnancy rate compared with those who received them in a down-regulation regimen; this difference was not explained by patient selection factors.     

Increasing the dose of human menopausal gonadotrophins on day of GnRH antagonist administration: randomized controlled trial

A significantly lower pregnancy rate following the gonadotrophin-releasing hormone (GnRH) antagonist protocol as compared with the long GnRH agonist protocol has been reported. The objective of this study was to investigate whether increasing the dose of gonadotrophins on the day of antagonist administration would increase the pregnancy rate. This study is an open labelled, randomized controlled trial and allocation was done using sealed envelopes. One hundred and fifty-one subfertile couples undergoing IVF/intracytoplasmic sperm injection (ICSI) cycles were included in the study. Ovarian stimulation was started on day 3 of the cycle, using 150-300 IU human menopausal gonadotrophin (HMG)/day. From day 8 onward, daily vaginal ultrasound and daily urinary LH estimation were performed. If a premature LH rise was detected, the cycle was cancelled. The antagonist (0.25 mg daily) was started when the leading follicle reached 15 mm in mean diameter and LH testing in urine was negative up to and including the day of human chorionic gonadotrophin (HCG) injection. Patients were randomized on the day of starting the antagonist into two groups: group A, 72 patients with no increase in HMG dose, and group B, 79 patients in whom the dose of HMG was increased by 75 IU on the day of antagonist administration, and continued till the day of HCG administration. The results showed no statistically significant difference between the groups regarding number of oocytes retrieved, embryos obtained, implantation rate, clinical pregnancy rate and multiple pregnancy rate. It was concluded that there is no clinical evidence for increasing the dose of HMG on the day of antagonist administration.     

A simplified universal approach to COH protocol for IVF: ultrashort flare GnRH-agonist/GnRH-antagonist protocol with tailored mode and timing of final follicular maturation

Recently, several new promising modifications have been introduced to clinical practice that may simplify and optimize IVF outcome. In the present opinion paper we present a simplified approach to controlled ovarian hyperstimulation protocol (COH), which combines the benefits of the ultrashort flare GnRH agonist/GnRH antagonist protocol and the personalized tailored mode and timing of ovulation triggering, aiming to improve IVF outcome while eliminating of severe OHSS.In patients at risk to develop severe ovarian hyperstimulation syndrome (OHSS), GnRH agonist (GnRHa) trigger if offered for final follicular maturation. While in those achieving ≥20 oocytes, the freeze all policy with the subsequent frozen-thawed embryo transfers (ET) is recommended, in those where less than 20 oocytes are retrieved, patients are re-evaluated 3 days after oocyte retrieval (day of ET) for signs of early moderate OHSS. If no early signs of OHSS developed, one embryo was transferred, and the patients are instructed to inject 1500 IU of HCG. In cases where signs of early moderate OHSS appear, the freeze all policy is recommended.In Patients not at risk to develop severe OHSS- three different modes of concomitant administration of both GnRHa and a standard bolus of hCG (5000–10,000 units) prior to oocyte retrieval were suggested. Standard hCG dose concomitant with GnRHa (dual trigger), 35–37 h before oocyte retrieval is offered to normal responders patients, resulting in improved oocyte/embryo quality and IVF outcome. GnRHa 40 h and standard hCG added 34 h prior to oocyte retrieval (double trigger), respectively are offered to patients demonstrating abnormal final follicular maturation despite normal response to COH. The double trigger results in significantly higher number of oocytes retrieved, higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, higher number of MII oocytes and proportion of MII oocytes per number of oocytes retrieved, with the consequent significantly increased number of top-quality embryos, as compared to the hCG-only trigger cycles. Standard hCG dose concomitant with GnRHa (dual trigger), 34 h before oocyte retrieval should be offered to poor responders patients, aiming to overcome premature luteinization, while achieving high yield of mature oocytes.Further studies are required to support this new concept prior to its implementation as a universal COH protocol to IVF practice.     

The impact of LH serum concentration on the clinical outcome of IVF cycles in patients receiving two regimens of clomiphene citrate/gonadotrophin/0.25 mg cetrorelix

Clomiphene citrate treatment with the association of gonadotrophins and the GnRH antagonist cetrorelix 0.25mg was analysed in two different stimulation protocols for IVF. In protocol I, 18 patients were sequentially stimulated with clomiphene citrate and gonadotrophins. In protocol II, 28 patients started the gonadotrophin injections during the clomiphene citrate administration. LH values significantly dropped after the first 0.25 mg cetrorelix injection in both protocols. A total of 22% and 7% of cycles were cancelled in protocols I and II, respectively, because of poor follicular development. The clinical pregnancy rate following embryo transfer was 18.1% in protocol I and 29.1% in protocol II. In two (11.1%) cycles stimulated according to protocol I and in eight (28.5%) cycles from protocol II, premature LH surges occurred. In patients with premature LH surge, significantly fewer metaphase II oocytes were obtained. The clinical pregnancy rate following embryo transfer was 12.5% in patients with surge compared with 29.6% in patients without. LH values were lower before HCG injection in patients who achieved pregnancy in the study cycle. In conclusion, sequential clomiphene citrate and gonadotrophin administration is not recommended for clomiphene citrate/gonadotrophin/cetrorelix 0.25 cycles. Cetrorelix 0.25 mg/day was associated with a high incidence of premature LH surges and premature LH surges were associated with an adverse cycle outcome.     

Pregnancies resulting from in vitro matured oocytes collected from women with regular menstrual cycle

Purpose: To demonstrate that human immature oocytes retrieved from women with regular menstrual cycles can undergo maturation and fertilization, and that the resulting embryos can establish pregnancies.Methods: Immature oocytes (n = 568) were retrieved from women with regular menstrual cycle. The intact immature oocytes (n = 506) were allowed to mature in YS medium supplemented with 70% human follicular fluid (hFF); the matured oocytes were fertilized with husband sperm. Two pronuclei oocytes were cocultured with cumulus cells in YS medium supplemented with 10% hFF until 2 or 3 days after insemination. The cleaved embryos were transferred in uteri.Results: Follicles were aspirated on Day 9.2 ± 5.3 of 63 natural cycles from 51 patients (mean age = 34.8 ± 4.0 years). The average number of retrieved immature oocytes was 9.0. The maturation rate was 74.3% (376/506). The two PN and cleavage rates were 72.6% (273/376) and 89.0% (243/273), respectively. Embryo transfer was achieved in 51 cycles and clinical pregnancy rate was 17.6% (9/51).Conclusions: The results suggest that in vitro matured oocytes can undergo fertilization and the resulting embryos may successfully lead to pregnancies. However, further research is needed to improve IVM technique to achieve success rate comparable to gonadotrophin stimulated cycles.