Triggering Of Oocyte Maturation Research Articles

In vitro viability and secretory capacity of human luteinized granulosa cells after gonadotropin-releasing hormone agonist trigger of oocyte maturation

To evaluate viability of luteinized granulosa cells obtained from patients triggered with either GnRH agonist or hCG and to assess the secretion of steroids and vascular endothelial growth factor (VEGF) by cultured luteinized granulosa cells in the presence or absence of hCG. Prospective, randomized controlled trial. University-based fertility center. A subset of patients who underwent a randomized trial involving GnRH agonist trigger after GnRH antagonist protocol vs. hCG trigger after pituitary suppression with GnRH agonist protocol. In vitro fertilization cycles. Proportion of apoptosis; basal and hCG-induced secretion of E(2), P, and VEGF by luteinized granulosa cells; follicular-fluid VEGF and luteal-phase serum E(2), P, and plasma VEGF concentrations. There were no differences in the proportion of granulosa/luteal cell apoptosis, follicular-fluid or luteal-phase plasma VEGF concentration, or basal culture media E(2), P, and VEGF concentrations between the two groups. Addition of hCG to the culture media significantly increased the P concentration in both groups, but there were no changes in E(2) or VEGF concentrations. Serum E(2) levels were lower at 5 and 9 days after GnRH agonist compared with hCG trigger. The granulosa/luteal cells obtained on the day of oocyte retrieval after GnRH agonist trigger are still viable and have the capacity to respond to hCG by increasing the secretion of steroids.

Factors that predict the probability of a successful clinical outcome after induction of oocyte maturation with a gonadotropin-releasing hormone agonist

To determine factors predicting cycle success after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in high-risk patients undergoing controlled ovarian stimulation with a gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist to induce oocyte maturation. Retrospective cohort study. University-based tertiary fertility center. Women who underwent a GnRH antagonist protocol during IVF-ICSI cycles and received a GnRH agonist for oocyte maturation. GnRH-agonist trigger. Clinical and ongoing pregnancy rates and any occurrence of ovarian hyperstimulation syndrome (OHSS). The serum luteinizing hormone (LH) level on the day of trigger of oocyte maturation was the single most important predictor of clinical pregnancy. Patients with a peak estradiol (E(2)) level ≥4,000 pg/mL also had statistically significant higher serum LH on the day of the GnRH-agonist trigger and had a higher clinical pregnancy rate compared with those with a peak E(2) level <4,000 pg/mL, although the two groups had comparable numbers of oocytes retrieved. No patients developed OHSS. Serum LH and E(2) levels ≥4,000 pg/mL on the day of the GnRH-agonist trigger are important predictors of success in patients at high risk of OHSS development. As none of the patients in this high-risk population developed OHSS, the GnRH-agonist trigger is effective in the prevention of this iatrogenic complication.

GnRH agonist for triggering of final oocyte maturation: time for a change of practice?

GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering. This narrative review is based on expert presentations and subsequent group discussions supplemented with publications from literature searches and the authors' knowledge. Moreover, randomized controlled trials (RCTs) were identified and analysed either in fresh IVF cycles with embryo transfer (ET), oocyte donation cycles or cycles without ET; risk differences were calculated regarding pregnancy rate and OHSS rate. In fresh IVF cycles with ET (9 RCTs) no OHSS was reported after GnRHa triggering [0% incidence in the GnRHa group: risk difference 5% (with 95% CI: -0.07 to 0.02)]. Importantly, the delivery rate improved significantly after modified luteal support [6% risk difference in favour of the HCG group (95% CI: -0.14 to 0.2)] when compared with initial studies with conventional luteal support [18% risk difference (95% CI: -0.36 to 0.01)]. In oocyte donation cycles (4 RCTs) the OHSS incidence is 0% [10% risk difference (95% CI: 0.02-0.40)]. GnRHa triggering is a valid alternative to hCG triggering, resulting in an elimination of OHSS. After modified luteal support there is now a non-significant difference of 6% in delivery rate in favour of hCG triggering.

Ovarian hyperstimulation syndrome prevention by gonadotropin-releasing hormone agonist triggering of final oocyte maturation in a gonadotropin-releasing hormone antagonist protocol in combination with a “freeze-all” strategy: a prospective multicentric study

To prospectively study ovarian hyperstimulation syndrome (OHSS) incidence and cumulative live birth rate in a cohort of patients at risk of OHSS undergoing ovarian stimulation in a GnRH antagonist protocol and receiving a GnRH agonist triggering followed by cryopreservation of all two pronuclei (2PN)-stage zygotes by two methods, vitrification or slow-cooling, for later ET. Prospective, clinical cohort study. Five IVF centers in Germany; time frame: June 2008 to June 2010. Fifty-one female patients undergoing IVF considered at risk of developing severe OHSS (≥20 follicles≥11 mm and/or E2 level≥4,000 pg/mL) after ovarian stimulation in a GnRH antagonist protocol. Triptorelin (0.2 mg SC) for triggering final oocyte maturation. All 2PN-stage zygotes were cryopreserved by vitrification or slow-cooling for later repetitive frozen-thawed ET. Severe OHSS incidence and cumulative live birth rate per patient. Of 51 patients, 1 patient (2%, 95% confidence [CI] 0.3%-10.3%) had zero oocyte retrieved, 1 patient did not undergo frozen-thawed ET, and 1 patient had no surviving oocyte after thawing. Thus, 48 patients underwent at least one frozen-thawed ET. The cumulative live birth rate was 37.3% (19/51, 95% CI 25.3%-51.0%). The live birth rate per first frozen-thawed ET was 5.9% (1/17, 95% CI 10.0%-27.0%) and 19.4% (6/31, 95% CI 9.2%-36.3%) in the slow-cooling and vitrification group, respectively (difference: 13.5%, 95% CI of the difference: -9.9%-31.1%). Three cases of OHSS II (3/51, 5.9%, 95% CI 2.0%-15.9%) and one early-onset case of OHSS III (1/51, 2%, 95% CI 0.3%-10.3%) occurred. Agonist triggering with cryopreservation is efficacious and safe, although a single case of a severe early-onset OHSS occurred.

Ovarian Hyperstimulation Syndrome Prevention Strategies: Use of Gonadotropin-Releasing Hormone Antagonists

The most serious complication of ovarian stimulation for in vitro fertilization is severe ovarian hyperstimulation syndrome (OHSS), a rare but potentially life-threatening condition. The present review discusses the place of gonadotropin-releasing hormone antagonists (GnRH-ant) in primary, secondary, and tertiary prevention of OHSS. Sound evidence indicates that the routine use of GnRH-ant instead of GnRH agonists (GnRHa) during ovarian stimulation drastically reduces the relative risk of OHSS. GnRH-ant are therefore useful for primary OHSS prevention, and an increased use of antagonists should help reduce the overall incidence of severe OHSS with its associated risks and complications. In patients on antagonist protocols identified to be at risk of developing severe OHSS, replacing human chorionic gonadotropin with GnRHa as a trigger of final oocyte maturation has been proposed as an effective measure of secondary prevention. A concept of combining GnRHa triggering with cryopreservation of all oocytes or embryos has yielded promising results as far as total avoidance of OHSS is concerned while providing a good chance of pregnancy for the patient in later frozen-thawed embryo transfers. In patients with early onset of OHSS, reinitiation of GnRH-ant in the luteal phase as a measure of tertiary prevention might lead to rapid regression of the syndrome; however only limited data on this new concept are available in the literature.

A novel method of luteal supplementation with recombinant luteinizing hormone when a gonadotropin-releasing hormone agonist is used instead of human chorionic gonadotropin for ovulation triggering: a randomized prospective proof of concept study

This pilot study investigates the role of luteal supplementation with recombinant LH in an attempt to reverse the poor reproductive outcome previously noticed after GnRH-agonist triggering of final oocyte maturation for IVF. Similar implantation rates were achieved with the novel recombinant LH luteal supplementation scheme compared with the standard luteal P protocol (25.0% vs. 26.7%, respectively). No cases of ovarian hyperstimulation syndrome (OHSS) were noticed in either group.

Prochloraz-induced Oocyte Maturation in Rainbow Trout (Oncorhynchus mykiss), a Molecular and Functional Analysis

In the present study, we aimed at characterizing the effect of prochloraz, an imidazole fungicide, on the oocyte meiotic maturation process in a freshwater teleost species, the rainbow trout (Oncorhynchus mykiss). Full-grown post-vitellogenic ovarian follicles were incubated in vitro with prochloraz, Luteinizing Hormone (LH), or a combination of prochloraz and LH. The occurrence of oocyte maturation was assessed by monitoring germinal vesicle breakdown (GVBD) after 62-h in vitro incubation. Experiments were repeated in presence of actinomycin D, cycloheximide, or trilostane. The effect of prochloraz on the production of 17,20β-dihydroxy-4-pregnen-3-one (17,20βP), the natural maturation-inducing steroid, was quantified by radioimmunoassay. In addition, the effect of prochloraz on ovarian expression of 12 genes was monitored by real-time PCR. Prochloraz (10(-5)M) administered alone was able to induce 100% GVBD in the most responsive females. The occurrence of GVBD observed after prochloraz stimulation of follicles originating from various females was similar and highly correlated with the occurrence of GVBD observed after stimulation with low LH concentration. In addition, oocyte maturation induced by LH or prochloraz was totally inhibited by actinomycin D, cycloheximide, and trilostane. Similarly to LH, prochloraz was able to trigger 17,20βP production by the ovarian follicle. Finally, prochloraz induced the overexpression of genes participating in 17,20βP production, intercellular communication, and paracrine control of preovulatory follicular differentiation such as igf, igf2, connexin 43, and 20β hydroxysteroid dehydrogenase (hsbd20). Together, our results demonstrate that prochloraz administered alone is able to trigger oocyte maturation through the induction of specific genes, some of them being also triggered by LH. Finally, our results clearly indicate that the effects of prochloraz and LH on oocyte maturation are synergistic.

Predictors of clinical pregnancy (CP) after elective single embryo transfer (eSBT)

OBJECTIVE: To identify clinical, biochemical, or embryologic factors associated with the establishment of a clinical pregnancy following the eSBT.DESIGN: Retrospective cohort.MATERIALS AND METHODS: First cycles of IVF where eSBT was performed from 01/06 to 12/09 were used. Inclusion criteria were age < 38 and FSH levels < 10. Patients requesting eSBT with at least 3 eight-cell embryos, grade 1 or 2 three days after oocyte retrieval had eSBT. CP was defined as fetal heart motion at 7-8 weeks. Multivariate regression modeling was performed to identify predictors of clinical pregnancy.RESULTS: Patients meeting inclusion criteria (n=99) were identified and 66 had a CP (66.7%). Factors not associated with CP included age (mean 32.4), BMI (mean 24.1 kg/m2), and infertility diagnosis (anovulation 14%, endometriosis 11%, male 23%, tubal 16%, unexplained 28%, other 7%), or day 3 FSH (mean 6.2 mIU/mL). There was a significant association of days of stimulation with CP on multivariate regression modeling (OR = 0.582, CI 0.370-0.916, p=0.02) with longer stimulation resulting in lower CP. This association reached maximum benefit at 9 days of stimulation. Although stimulation protocol did not affect CP, GnRH agonist (GnRHa) trigger for oocyte maturation was negatively associated with CP in multivariate regression modeling (OR = 0.069, CI 0.020-0.239, p< 0.01). In antagonist cycles, hCG trigger resulted in higher CP (45/54, 83.3%) than GnRHa trigger (6/22, 27.3%). Oocyte and embryo parameters failing to affect CP included % mature, germinal vesicle, degenerate, or dark/grainy oocytes, multinucleated embryos on day 2, embryos compacted on day 3; and day 3 embryo grading of blastocyst replaced, # of embryos 7 cell grade I-IV or greater, or # of cryopreserved embryos.CONCLUSION: In this group of patients, prolonged ovarian stimulation is predictive of lower success of eSBT. While antagonist cycles did not result in lower CP, utilization of GnRH-a to trigger oocyte maturation has a significantly negative impact on CP. OBJECTIVE: To identify clinical, biochemical, or embryologic factors associated with the establishment of a clinical pregnancy following the eSBT. DESIGN: Retrospective cohort. MATERIALS AND METHODS: First cycles of IVF where eSBT was performed from 01/06 to 12/09 were used. Inclusion criteria were age < 38 and FSH levels < 10. Patients requesting eSBT with at least 3 eight-cell embryos, grade 1 or 2 three days after oocyte retrieval had eSBT. CP was defined as fetal heart motion at 7-8 weeks. Multivariate regression modeling was performed to identify predictors of clinical pregnancy. RESULTS: Patients meeting inclusion criteria (n=99) were identified and 66 had a CP (66.7%). Factors not associated with CP included age (mean 32.4), BMI (mean 24.1 kg/m2), and infertility diagnosis (anovulation 14%, endometriosis 11%, male 23%, tubal 16%, unexplained 28%, other 7%), or day 3 FSH (mean 6.2 mIU/mL). There was a significant association of days of stimulation with CP on multivariate regression modeling (OR = 0.582, CI 0.370-0.916, p=0.02) with longer stimulation resulting in lower CP. This association reached maximum benefit at 9 days of stimulation. Although stimulation protocol did not affect CP, GnRH agonist (GnRHa) trigger for oocyte maturation was negatively associated with CP in multivariate regression modeling (OR = 0.069, CI 0.020-0.239, p< 0.01). In antagonist cycles, hCG trigger resulted in higher CP (45/54, 83.3%) than GnRHa trigger (6/22, 27.3%). Oocyte and embryo parameters failing to affect CP included % mature, germinal vesicle, degenerate, or dark/grainy oocytes, multinucleated embryos on day 2, embryos compacted on day 3; and day 3 embryo grading of blastocyst replaced, # of embryos 7 cell grade I-IV or greater, or # of cryopreserved embryos. CONCLUSION: In this group of patients, prolonged ovarian stimulation is predictive of lower success of eSBT. While antagonist cycles did not result in lower CP, utilization of GnRH-a to trigger oocyte maturation has a significantly negative impact on CP.

Endometrium receptivity in in-vitro maturation (IVM) treatment

OBJECTIVE: Transforming endometrium from a mid-follicular to an effective luteal environment in IVM-cycles is challenging. Failure to obtain a receptive endometrium may underlie unsuccessful implantation in IVM. Research focussing on endometrium histology in IVM cycles is scarce. DESIGN: A prospective cohort pilot study in 41 normo-ovulatory volunteers and 9 with PCOS. MATERIALS AND METHODS: Oocytes were matured and fertilized for research purposes. No embryos were transferred, but endometrial development was investigated. Endometrial priming consisted of 450 IU uFSH, followed by 6 mg daily transdermal estradiol gel (10 mg if endometrium thickness was < 8 mm) and 600 mg daily vaginal progesterone. 20 volunteers received a final oocyte maturation trigger using 5000 IU hCG; 30 received no such trigger. Endometrium receptivity was assessed using vaginal ultrasound scanning and histological analysis of endometrium biopsies performed during the luteal phase of an IVM-cycle (on either day 4, 5, 6 or 7 after oocyte retrieval). RESULTS: Endometrium histology did not correlate with endometrium thickness and was not significantly influenced by hCG-triggering. According to Noyes' criteria, 40,0 % (14/34) resp. 37,5 % (3/8) of representative samples from non-PCOS reps. PCOS volunteers showed a receptive endometrium. Overall, 56,3 % had an endometrium maturation delay exceeding 2 days, of which 33,3 % showed no secretory changes at all. CONCLUSION: A receptive endometrium is a prerequisite for successful implantation. In IVM-cycles, the results of our pilot study show a high incidence of secretory defects in spite of standard hormonal endometrial priming. Further research is needed to establish an optimal hormonal treatment protocol in IVM-cycles and to identify molecular markers that indicate a competent endometrium.

Recombinant versus urinary human chorionic gonadotropin for final oocyte maturation triggering in IVF/ICSI cycles. Cochrane systematic review and meta-analysis

OBJECTIVE: to assess the safety and efficacy of subcutaneous rhCG and high dose rLH compared with intramuscular uhCG for inducing final oocyte maturation triggering. DESIGN: systematic review and meta-analysis of RCTs comparing r HCG with u HCG for final oocyte maturation triggering in IVF/ICSI cycles. MATERIALS AND METHODS: Primary outcomes were live birth rate/ongoing pregnancy and OHSS incidence per randomised woman. Secondary outcomes were miscarriage rate, number of oocytes retrieved and treatment related side effects. We searched MEDLINE, EMBASE, Science Direct, Cochrane Library and databases of abstracts (until January 2010). Two review authors independently scanned the abstracts, identified relevant papers, assessed inclusion and trial quality and extracted relevant data. Validity was assessed in terms of method of randomisation, allocation concealment and outcomes. RESULTS: 14 RCTs (n=2306) were identified, eleven studies (n=1827) compared rhCG and uhCG and three studies (n= 479) compared rhLH and uhCG. There was no statistically significant difference between rhCG vs uhCG regarding the ongoing pregnancy/ live birth rate (6 RCTs: OR 1.04, 95% CI 0.79 to 1.39; P = 0.83, I2 = 0%), or incidence of OHSS ((3 RCTs; OR 1.49, 95% CI 0.37 to 4.10; P= 0.37, I2 = 0%). There was statistically significant difference regarding the number of oocytes retrieved in favour of u HCG (9 RCTs: WMD 0.42, 95% CI -0.57 to -0.27, P <0.000, I2= 80%). rhCG was associated with significant reduction in the incidence of local site reactions and other minor adverse effects (3 RCTs: OR 0.39, 95% CI 0.25 to 0.61, P= 0.81, I2 = 0%). CONCLUSION: There is no evidence of difference in clinical outcomes between urinary and recombinant gonadotrophins for final oocyte maturation triggering, but there is an evidence of statistically difference regarding the number of oocytes retrieved in favour of u HCG and adverse events in favour of r HCG.

The endocrine profile of in-vitro maturation treatment cycles

OBJECTIVE: In-vitro maturation treatment encompasses oocyte retrieval in the mid-follicular phase which impacts on luteal function and thus on endometrial competence. Here, we describe the dynamics of serum steroid levels in IVM-cycles and their influence on endometrial quality. DESIGN: A prospective cohort pilot study in 41 normo-ovulatory volunteers and 9 with PCOS. MATERIALS AND METHODS: 20 volunteers received a final oocyte maturation trigger using 5000 IU hCG; 30 received no such trigger. Endometrial priming consisted of 450 IU uFSH, followed by 6 mg daily transdermal estradiol gel (10 mg if endometrium thickness was < 8 mm) and 600 mg daily vaginal progesterone. Serum levels of progesterone (P) and estradiol (E2) were measured on cycle day 8, on the day of egg retrieval and during the luteal phase. Correlations were studied between endocrine serum levels and the endometrial histology. RESULTS: Serum progesterone levels did not differ between subgroups. Overall, hCG-triggering was correlated with decreasing E2 levels during the luteal phase. In PCOS, but not in normo-ovulatory volunteers, luteal phase E2 levels were significantly higher in volunteers with an in-phase endometrium than in those with a secretory delay. Normo-ovulatory volunteers with a competent endometrium who had not received an hCG-trigger had more than two-fold increased luteal phase E2 levels as compared to E2 levels at egg retrieval, whereas in those with a maturation delay E2 levels had dropped significantly after egg retrieval. CONCLUSION: The exact mechanisms underlying improper luteal function after egg retrieval in IVM-treatment are still open for speculation. The results of our pilot study indicate that distinct endocrine patterns may give clues to explain endometrial histological findings in IVM-cycles. Improper luteinisation of follicles may underlie rising estradiol levels after egg retrieval that are associated with a receptive endometrium after substitution therapy.

Low-dose human chorionic gonadotropin versus estradiol/progesterone luteal phase support in gonadotropin-releasing hormone agonist–triggered assisted reproductive technique cycles: understanding a new approach

It remains unclear how GnRH agonist (GnRHa) triggering affects the luteal phase, so we investigated the luteal phase after GnRHa triggering, supported with conventional E(2)/P with or without low-dose hCG. E(2)/P support, compared with low-dose hCG, induced a shorter luteal phase (11.2 ± 1.1 vs. 15.0 ± 1.6 days) and fewer subjective complaints (0 vs. 42%), whereas hCG caused more free fluid accumulation and enlarged ovaries than E(2)/P alone. Steroids and low-dose hCG differentially affected corpus luteum function, ovarian size, free fluid accumulation, and patient comfort.

LH (as HCG) and FSH surges for final oocyte maturation: sometimes it takes two to tango?

Until now, clinicians have been relying solely on LH activity-dependent triggering of final oocyte maturation and thus taken it for granted that the natural midcycle FSH surge is biologically redundant. However, it is time to question this paradigm. Evidence from clinical studies hint that in a yet-to-be-defined subset of patients, dual LH and FSH surge is advantageous compared with LH-only surge in the form of human chorionic gonadotrophin (HCG) trigger. Dual surge can be triggered by a bolus of gonadotrophin-releasing hormone agonist causing a flare-up of both endogenous LH and FSH, resembling the natural midcycle surge of gonadotrophins. HCG given in parallel secures adequate exposure to LH activity. Further research is needed to characterize the patients in whom FSH surge is needed for proper resumption of the oocyte meiotic process.

Effect of oral contraceptive pills upon IVF outcomes of patients under a short GnRH agonist protocol

To determine the link between oral contraceptive pill (OCP) use and IVF/ICSI treatment outcomes under a short GnRH agonist protocol. A total of 186 patients (one cycle each patient) received a short GnRH agonist protocol at Day 2 of menstrual cycle for IVF/ICSI. Among them, 83 patients took OCP pre-treatment prior to the stimulation protocol (OCP group) and 103 patients received no OCP (non-OCP group). The triggering of final oocyte maturation was performed with 10 000 IU of hCG. The ongoing pregnancy rates per started cycle in the non-OCP group and OCP group were 27.8% and 12.7% (P < 0.05) respectively. The clinical pregnancy rate and embryo implantation rate were significantly reduced in OCP group (clinical pregnancy rate 16.5%, implantation rate 11.2%) as compared with non-OCP group (32.2% and 19.9%, P < 0.05). The endometrium on hCG day was thicker in non-OCP group than OCP group (9.5 mm vs 8.7 mm, P < 0.05). Pretreatment with OCP, as compared with initiation of stimulation at Day 2 of cycle in patients treated with GnRH-a short protocol antagonist appears to be associated with a significant difference in ongoing pregnancy rates per started cycle.

Cumulative live birth rates after GnRH-agonist triggering of final oocyte maturation in patients at risk of OHSS: A prospective, clinical cohort study

Objectives To prospectively study the incidence of OHSS, live birth likelihood and neonatal outcome after GnRH-agonist triggering of final oocyte maturation and vitrification of all pronucleate (2PN) oocytes for later frozen–thawed embryo transfer (FRET) in an OHSS-risk population. Study design Prospective, clinical cohort study (12/2004–5/2009). Forty patients undergoing ovarian stimulation in a GnRH-antagonist protocol and at risk of developing severe OHSS underwent triggering with 0.2 mg triptorelin and elective vitrification of all 2PN-oocytes for later frozen–thawed embryo transfer. Results The incidence of OHSS was 0% (0/40; 95% confidence interval: 0.0–6.4%). Thirty-nine patients underwent 87 FRETs (mean number of FRETs per patient: 2.2 ± 1.6; range: 1–7). The cumulative live birth rate per patient was 35.0% (14/40; 95% confidence interval: 23.9–48.0%). Mean time-to-conception resulting in live birth after agonist triggering was 24.2 (±17.1; range: 9–67) weeks. Nine healthy singletons and five twins were born. Conclusions A treatment algorithm combining agonist trigger with vitrification of all 2PN-oocytes is feasible and safe, and provides patients with a good cumulative chance of live birth.

Gonadotropin-releasing hormone agonist to induce final oocyte maturation prevents the development of ovarian hyperstimulation syndrome in high-risk patients and leads to improved clinical outcomes compared with coasting

Ninety-four women undergoing IVF with peak E2 level>4000 pg/mL received leuprolide acetate (LA) trigger (LA trigger group) or had gonadotropins withheld for one or more days (coasting group) followed by hCG trigger, unless cycle cancellation occurred. There were no cases of ovarian hyperstimulation syndrome in either group, and the LA trigger group had significantly more oocytes retrieved (26.9+/-9.5 vs. 17.7+/-9.3) P<0.001, more normally fertilized oocytes (15.0+/-7.8 vs. 10.3+/-6.3) P=0.01, and higher clinical and ongoing pregnancy rates than the coasting group (52.5% vs. 27.2%; 49.2% vs. 24.2%, P=0.02 for both comparisons, respectively).

GnRHa to trigger final oocyte maturation: a time to reconsider

Recently GnRH antagonist protocols for the prevention of a premature LH surge were introduced, allowing final oocyte maturation to be triggered with a single bolus of a GnRH agonist (GnRHa). GnRHa is as effective as hCG for the induction of ovulation, and apart from the LH surge a FSH surge is also induced. Until recently, prospective randomized studies reported a poor clinical outcome when GnRHa was used to trigger final oocyte maturation in IVF/ICSI antagonist protocols, presumably due to a luteal phase deficiency, despite standard luteal phase supplementation with progesterone and estradiol. As GnRHa triggering of final oocyte maturation could possess advantages over hCG triggering in terms of a reduced if not eliminated risk of ovarian hyperstimulation syndrome (OHSS) and the retrieval of more mature oocytes, the challenge has been to rescue the luteal phase. In the literature now several studies report a luteal phase rescue with a reproductive outcome comparable to that of hCG induced final oocyte maturation. Although more research is needed, GnRHa triggering is now a valid alternative with potential benefits.

Improved monitoring of ovarian stimulation using 3D transvaginal ultrasound plus automated volume count

Two-dimensional transvaginal ultrasound (2D) is typically performed to monitor follicle growth in IVF and to determine the optimal time for administering human chorionic gonadotrophin. However, 2D only provides an approximation of the real volume of follicles and therefore cannot be used to guarantee standards for follicular measurement. The automated measurement of follicular size in three dimensions (3D) using a software programme that identifies and quantifies hypoechoic regions within a 3D dataset might provide an objective, fast, valid and reliable standard for such measurements. A prospective controlled study (group I: 20 patients, 2D; group II: 20 patients, 3D) investigated how the criteria for triggering oocyte maturation that are normally used in 2D compare to the new and more accurate method of measuring follicles using 3D-based automated volume count. Significantly more oocytes were fertilized (group 1: 7.1 +/- 4.5, group 2: 11.5 +/- 6.4; P < 0.03) when using 3D technology and automated volume count. The study assumes that the automated volume count more closely mirrors the biological reality, which means that it can also be used to guarantee the quality standards established by the European Union directive on tissues and cells (2004/23/EC). This new technology therefore holds great promise of becoming the new standard for monitoring follicular growth in IVF.

Natural cycle IVF is an excellent treatment option for women with advanced age

OBJECTIVE: Women with advanced age have poor ART outcome. Controlled ovarian hyperstimulation is associated with multiple side effects. In this study, we are analyzing the outcome of nature cycle IVF in treating this group of patients. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: After abtaining IRB approval, we reviewed nature cycle IVF data in our clinic from January to December 2008. All patients between 38 to 45 year old were analyzed. In nature cycle IVF, patients were closely monitored for their folliclular growth. When dominant follicle reachs 17-19 mm, patients were given GnRH agonist for triggering oocyte maturation. Oocyte retrievals were performed 32-34 hours later. Single embryo transfers were performed at 4-cell stage (day 2) or blastocyst (day 5). Clinical pregnancy was confirmed after fetal cardiac activity noted by ultrasound. We devided patients into 3 groups: A (age 38-40); B (age 41-43) and C (age 44 and 45). Oocyte retrieval rate, fertilization rate, embryo cleavage rate and clinical pregnancy rate were analyzed in each group. Chi-Square test was used for statistical analysis, and P<0.05 was considered statistically significant. RESULTS: Oocyte retrieval rates in each groups were A: 66.0% (401/608), B: 61.6% (252/409); and C: 56.4% (102/181), respectively. Fertilization rates were A: 77.8% (312/401), B: 81.3% (205/252), and C: 76.5% (78/102), respectively. Embryo cleavage rates were A: 71.1% (285/401), B: 71.4% (180/252), and C: 66.7% (66/102), respectively. Clinical pregnancy rates per embryo transfer were A: 29.8% (57/191), 20.8% (20/96), and 6.5% (2/31), respectively. No statistical differences were found among all groups except the clinical pregnancy rate. Patients with age 44-45 had significantly lower clinical pregnancy rate (P<0.05). CONCLUSIONS: Women with advanced age are associated with poor ovarian reserve and they also have poor ART outcome with conventional IVF. Nature cycle IVF provides an excellent option for this group of patients.

GnRHa to trigger final oocyte maturation: a time to reconsider

Recently GnRH antagonist protocols for the prevention of a premature LH surge were introduced, allowing final oocyte maturation to be triggered with a single bolus of a GnRH agonist (GnRHa). GnRHa is as effective as hCG for the induction of ovulation, and apart from the LH surge a FSH surge is also induced. Until recently, prospective randomized studies reported a poor clinical outcome when GnRHa was used to trigger final oocyte maturation in IVF/ICSI antagonist protocols, presumably due to a luteal phase deficiency, despite standard luteal phase supplementation with progesterone and estradiol. As GnRHa triggering of final oocyte maturation could possess advantages over hCG triggering in terms of a reduced if not eliminated risk of ovarian hyperstimulation syndrome (OHSS) and the retrieval of more mature oocytes, the challenge has been to rescue the luteal phase. In the literature now several studies report a luteal phase rescue with a reproductive outcome comparable to that of hCG induced final oocyte maturation. Although more research is needed, GnRHa triggering is now a valid alternative with potential benefits.