Growth hormone supplementation improves implantation and pregnancy productivity rates for poor-prognosis patients undertaking IVF

In a sequential crossover study of IVF conducted from 2002 to 2006, growth hormone (GH) supplementation was assessed in poor-prognosis patients, categorized on the basis of past failure to conceive (mean 3.05 cycles) due to low response to high-dose stimulation (<3 metaphase II oocytes) or poor-quality embryos. Pregnancy rates in both fresh and frozen transfer cycles and the total productivity rates (fresh and frozen pregnancies per egg collection) were compared. In all, 159 patients had 488 treatment cycles: 221 with GH and 241 without GH. These cycles were also compared with 1572 uncategorized cycles from the same period. GH co-treatment significantly improved the clinical pregnancy rate per fresh transfer (P < 0.001) as well as per frozen–thawed embryo derived from GH cycles (P < 0.05) creating a highly significant productivity rate (P < 0.001). The effect was significant across all age groups, especially in younger patients, and was independent of stimulation modality or number of transfers. GH cycles resulted in significantly more babies delivered per transfer than non-GH cycles (20% versus 7%; P < 0.001) although less than the uncategorized cycles (53%). The data uniquely show that the effect of GH is directed at oocyte and subsequent embryo quality.     

HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation

The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n = 986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up-to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3–58.1%) for HP-HMG and 44.6% (40.2–49.0%) for rFSH (OR 1.44, 95% CI 1.12–1.85; P < 0.005). The mean costs per IVF treatment for HP-HMG and rFSH were £5393 (£5341–5449) and £6269 (£6210–6324), respectively (number needed to treat to fund one additional treatment was seven; P < 0.001). With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was £11,157 (£11,089–11,129) and £14,227 (£14,183–14,222) with rFSH (P < 0.001). The cost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis.     

Freeze-all: enhanced outcomes with cryopreservation at the blastocyst stage versus pronuclear stage using slow-freeze techniques

This retrospective cohort study compared outcomes from transfer of embryos cryopreserved at the pronuclear versus blastocyst stage following ‘freeze-all’ IVF cycles without fresh transfer for 87 consecutive IVF patients <40 years, who underwent cryopreservation of all viable embryos followed by at least one subsequent frozen embryo transfer (FET) between January 2003 and July 2007. Cryopreservation of all embryos from one oocyte retrieval was performed at either the pronuclear (1.5 mol/l propanediol and 0.1 mol/l sucrose) (group A) or blastocyst (10% glycerol) (group B) stage. Main outcome measures included survival, live birth and implantation rates. A total of 110 FET cycles were analysed. Live birth and implantation rates observed after the first FET were significantly higher (P = 0.025 and P = 0.002) in group B (67.7% and 40.8%) than in group A (41.1% and 21.5%) despite a higher survival rate in group A. After two FET cycles, 32.1% of group A had not conceived despite thaw of all available embryos, compared with 6.5% of group B. When freeze-all is necessary, blastocyst cryopreservation leads to higher implantation and live birth rates compared with pronuclear-stage cryopreservation despite lower survival rates. Prolonged embryo culture may allow for more optimal embryo selection.     

Are US results for assisted reproduction better than the rest? Is it a question of competence or policies?

A comparison of nationally published 2006 data from the USA, UK and Australia and New Zealand (ANZ) was performed. Although live births/cycle was higher in USA, live birth/embryo transferred was significantly higher in ANZ (18.2%) compared with both USA and UK (13.8%) (P < 0.001). The multiple rates were significantly lower in ANZ (12.0%) compared with USA (30.7%) and UK (25.2%) (P < 0.001). The incidence of oocyte donation was significantly higher in the USA (11.1%) than in ANZ (2.8%) and UK (3.9%) (P < 0.001). There was significantly higher cycle cancellation in USA (11.5%) compared with the UK (6.8%) and ANZ (9.5%) (P < 0.001). The incidence of frozen embryo transfer cycles was significantly higher in ANZ (59%) compared with both UK (24%) and USA (22%) (P < 0.001). The total live birth rate from fresh and frozen cycles for the same year was significantly higher in ANZ at 32.0% compared with the UK at 28.8% (P < 0.001) with half the multiple rate. It is argued that the USA’s higher success rates are explained by policy (transferring higher number of embryos) and selection issues (cancelling or avoiding poor responders) rather than being a matter of clinical competence.     

Septate,subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI

A retrospective matched-control study to evaluate the effect of uterine anomalies on pregnancy rates after 2481 embryo transfers in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group of 289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of a uterine septum was compared with two consecutive embryo transfers in the control group. Groups were matched for age, body mass index, ovarian stimulation, embryo quality, IVF or ICSI and infertility aetiologies. Number of embryos transferred, embryo quality and absence of uterine anomalies significantly predicted the pregnancy rates in the study group: odds ratios (OR) 1.7, 2.6 and 2.5, respectively (P < 0.001). Pregnancy rates after embryo transfer before hysteroscopic metroplasty were significantly lower, both in women with subseptate and septate uterus and in women with arcuate uterus compared with controls. If two or three embryos with at least one best-quality embryo were transferred, the differences were 9.6% versus 43.6%, OR 7.3 (P < 0.001) and 20.9% versus 35.5%, OR 2.1 (P < 0.03), respectively. Differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR 32 (P < 0.001) and 3.0% versus 30.4%, OR 14 (P < 0.001). After surgery, the differences disappeared.This retrospective matched control study evaluated the influence of septate, subseptate and arcuate uterus on pregnancy and live birth rates after 2481 in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group included 827 embryo transfers (289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of uterine septum ans was compared with two consecutive mebryo transfers in the control group. Both groups were matched by age, body mass index, stimulation protocol, quality of embryos, use of IVF or ICSI, and infertility aetiologies. Multivariate logistic regression analysis of the study group showed that the number of embryos, embryo quality and the absence of uterine anomalies significantly predicted the pregnancy rates: odds ratios (OR) 1.7, 2.6, and 2.5, respectively (P < 0.001). The pregnancy and live birth rates before surgery were lower compared with controls, both in women with subseptate or septate uterus and in women with arcuate uterus. If two or three embryos with at least one best quality embryo were transferred, the differences in terms of pregnancy rates were 9.6% versus 43.6%, OR = 7.3 (P < 0.001) and 20.9% versus 35.5%, OR = 2.1 (P < 0.03), respectively. The differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR = 32 (P < 0.001) and 3.0% versus 30.4%, OR = 14 (P < 0.001). After surgery, the differences disappeared. Negative impact of uterine anomalies on pregnancy and on live birth rates are two important arguments for treating uterine anomalies in infertile women.     

Blastocyst culture and cryopreservation to optimize clinical outcomes of warming cycles

Surplus embryos available for cryopreservation in fresh cycles are considered as having good potential for future use. However, the optimal stage of embryo cryopreservation remains unclear. In this study, 1190 patients with surplus embryos on day 3 were divided into two groups: cleavage-stage embryo cryopreservation (control group) and blastocyst cryopreservation (blastocyst group). The clinical outcomes of the subsequent warming cycles were evaluated. The proportion of cycles with blastocyst formation was 73.8% in the blastocyst group. Although in the blastocyst group, the cancellation rate of blastocyst transfer was increased due to lack of blastocysts available for cryopreservation, the blastocyst group achieved significantly higher rates of clinical pregnancy/cycle (43.2% versus 34.9%; P = 0.003), pregnancy/transfer (59.5% versus 35.4%; P < 0.001) and implantation (46.5% versus 22.2%; P < 0.001) from the first warming cycle compared with the control group. In an embryo-number classified analysis, the clinical pregnancy rate was also higher in the blastocyst group. However, the cumulative pregnancy was similar between the two groups. Blastocyst culture as an embryo selection tool will not improve embryo viability but it will help patients to achieve pregnancy more quickly. Extended culture of surplus embryos to the blastocyst stage for cryopreservation optimizes the clinical outcomes.Surplus embryos available for cryopreservation in fresh cycles have been considered as having good potential for future use. However, it remains unclear whether cleavage-stage embryo cryopreservation on day 3 or further extended culture with blastocyst cryopreservation on day 5 or 6 is of most benefit to patients. This prospective study was undertaken to evaluate the clinical outcomes of vitrified–warmed embryo transfer cycles according to cryopreservation of embryos at different stages. The study enrolled 1190 patients with surplus embryos on day 3, who were divided into two groups: cleavage-stage embryo cryopreservation (control group) and blastocyst cryopreservation (blastocyst group). The proportion of cycles with blastocyst formation in the blastocyst group was 73.8%. Although the cancellation rate of blastocyst transfer in the blastocyst group was increased due to lack of blastocysts available for cryopreservation, the blastocyst group achieved significantly higher rates of clinical pregnancy/cycle (43.2% versus 34.9%; P = 0.003), clinical pregnancy/transfer (59.5% versus 35.4%; P < 0.001) and implantation (46.5% versus 22.2%; P < 0.001) from the first warming cycle as compared with the control group. In an embryo-number classified analysis, the clinical pregnancy rate was also higher in the blastocyst group. However, the cumulative pregnancy was similar between the two groups. In conclusion, blastocyst culture as an embryo selection tool will not improve embryo viability but it will help patients to achieve pregnancy more quickly. Extended culture of surplus embryos to the blastocyst stage for cryopreservation optimizes the clinical outcomes of the subsequent warming cycles.     

Is the Flexible GnRH Antagonist Protocol Better Suited for Fresh eSET Cycles?

ObjectiveThis study was performed to evaluate the efficacy of the flexible GnRH antagonist protocol in comparison with the long GnRH agonist protocol in elective single embryo transfer (eSET) practice. It was conducted in a publicly funded in vitro fertilization program.MethodsWe performed a prospective cohort analysis of data from a private infertility clinic from August 2010 to August 2011. Three hundred fourteen women with normal ovarian reserve and undergoing fresh eSET cycles were included. Sixty-four women underwent follicular stimulation using a flexible GnRH antagonist protocol, and 250 underwent stimulation with a standard long mid-luteal GnRH agonist protocol.ResultsImplantation rates (35.9% in the GnRH antagonist group and 29.6% in the GnRH agonist group, P = 0.5) and ongoing pregnancy rates (32.8% in the GnRH antagonist group and 28.8% in the GnRH agonist group, P = 0.5) were equivalent in both groups. The duration of stimulation (9.8 ± 2 days vs. 10.7 ± 1.8 days, P < 0.001) and total FSH dose required (2044 vs. 2775 IU, P < 0.001) were lower in the GnRH antagonist group than in the GnRH agonist group. The number of mature oocytes (6.0 vs. 10.0, P < 0. 001) and number of embryos (5.0 vs. 7.0, P < 0.001) were also lower in GnRH antagonist group. However, the number of embryos cryopreserved was similar in both groups (median 2.0, P = 0.3).ConclusionIn women undergoing in vitro fertilization, the flexible GnRH antagonist protocol yields implantation and ongoing pregnancy rates that are similar to the long GnRH agonist protocol, and requires lower doses of gonadotropins and a shorter duration of treatment. The flexible GnRH antagonist protocol appears to be the protocol of choice for an eSET IVF program.     

Planar embryos have poor prognosis in terms of blastocyst formation and implantation

Normally, day-2 embryos show a crosswise arrangement of four cells with three blastomeres lying side by side. Cleavage anomalies include embryos that are characterized by a particular planar constellation of four blastomeres with presumed incomplete cleavage. Since little is known on the developmental fate of such conceptuses, within a 10-month period all consecutive patients were screened for day-2 planar embryos. A total of 64/2070 embryos with suboptimal blastomere configuration were detected (3.1%). In conventional IVF, planar embryos were significantly less frequent (0.7%) as compared with intracytoplasmic sperm injection (2.8%; P < 0.05) and cases of testicular sperm extraction (5.4%; P < 0.01). Interestingly, embryos with a cleavage anomaly showed better morphology both on day 2 (P < 0.005) and day 3 (P < 0.001). In contrast, blastocyst formation (P < 0.001) and blastocyst quality (P = NS) was higher in tetrahedral embryos. There was a significant increase in implantation rate if tetrahedral embryos could be transferred compared with when planar embryos had to be transferred (P < 0.01). It may be postulated that, in planar embryos, the mitotic spindle might have been affected, e.g. sperm centrosome composition or function, which in turn might have led to the observed cleavage anomaly.Normally, day-2 embryos show a crosswise arrangement of four cells with three blastomeres lying side by side. Cleavage anomalies include more planar embryos that are characterized by a particular flat constellation of four blastomeres with presumed premature cleavage (like a tetrafoliate clover). Since little is known on the developmental fate of such embryos within a 10-month study period, all consecutive patients were screened for the presence of day-2 planar embryos (study group). A total of 64 (out of 2070) embryos with abnormal blastomere configuration were detected (3.1%). Interestingly, in conventional IVF (0.7%), the presence of planar embryos was significantly less frequent as compared with intracytoplasmic sperm injection (2.8%; P < 0.05) and cases of testicular biopsy (5.4%; P < 0.01). Embryos from the study group showed better morphology both on day 2 (P < 0.005) and day 3 (P < 0.001). In contrast, blastocyst formation (survival to day 5 of preimplantation development) was higher in the normally cleaved control group (P < 0.001) and so was blastocyst quality; however, the latter parameter did not reach level of significance. This was also reflected in a significantly higher implantation rate in the control group (P < 0.01). Based on present data, it may be postulated that, in planar embryos, the mitotic spindle (which involves the sperm centrosome) might have been affected, which in turn might have led to an incomplete cleavage.     

Progesterone elevation on the day of HCG administration may affect rescue ICSI

To investigate the relationship between serum progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration and rescue intracytoplasmic sperm injection (ICSI), a total of 9858 patients who underwent IVF or rescue ICSI were retrospectively analysed. The results showed a significant difference in serum progesterone concentration on the day of HCG administration between the IVF group and rescue ICSI group (P < 0.01). Multivariate logistic regression showed that progesterone concentration was positively and significantly associated with rescue ICSI (OR 1.297, 95% CI 1.153–1.460, P < 0.001). Moreover, an increased rescue ICSI rate was associated with progressively higher progesterone concentrations in all cycles. In addition, patients with progesterone >1.5 ng/ml demonstrated a significantly higher rescue ICSI rate compared with patients with progesterone concentration ⩽1.5 ng/ml (P < 0.05). In conclusion, elevated progesterone on the day of HCG administration had an adverse effect on oocyte fertilization; thus, greater attention should be paid to these patients in an attempt to avoid fertilization failure, especially when progesterone is >1.50 ng/ml.For the issue of oocytes fertilization, most literatures have found the presence of a negative association between P elevation and fertilization. They suggested that P elevation may only influence the endometrium, leading to impaired endometrial receptivity and had no adverse effect on the fertilization of oocytes. On the contrary, we enrolled 9,858 fresh cycles and found elevated P had an adverse effect on the oocytes fertilization, especially if the P concentration >1.50 ng/mL. It is the first report about the relationship between the rescue ICSI and serum P levels.     

Successful birth following transfer of frozen–thawed embryos produced from in-vitro matured oocytes

It is well established that ovarian hyperstimulation syndrome (OHSS) is more frequent in patients with polycystic ovarian syndrome. In-vitro maturation (IVM) of immature oocytes presents a potential alternative for the fertility treatment and prevention of OHSS for these patients. This report describes the case of a 26-year old woman with a successful pregnancy and delivery following the transfer of frozen–thawed embryos derived from in-vitro matured oocytes. She had three failed cycles of ovarian stimulation (using low-dose step-up gonadotrophin protocol) with or without intrauterine insemination cycles, an ovulation-induction cycle with luteal long protocol, two fresh IVM cycle and one frozen–thawed IVM cycle. During the IVF cycle, she developed moderate OHSS and required hospitalization for 3 weeks. Following four unsuccessful IVF or IVM cycles, 15 months after the last cryopreservation, six fertilized oocytes were thawed for a scheduled embryo transfer. Following thawing, four fertilized oocytes survived and cleaved. Four frozen–thawed embryos were transferred. Six weeks after embryo transfer an ongoing intrauterine single pregnancy with fetal heartbeat was confirmed by transvaginal ultrasound. An uneventful pregnancy and delivery via Caesarean section at 39 weeks resulted in the birth of a normal healthy infant.     

Prediction of IVF/ICSI outcome based on the follicular output rate

This study assessed the true accuracy of follicular output rate (FORT) as a prognostic indicator of response to FSH and reproductive competence after IVF/intracytoplasmic sperm injection. A total of 1643 cycles, including 140 polycystic ovary syndrome (PCOS) patients who underwent ovarian stimulation, were studied. FORT was calculated as the ratio of preovulatory follicle count on the day of stimulation × 100/small antral follicle count (3–10 mm in diameter) at baseline. Low, medium and high FORT groups were defined according to tertile values. Among 1503 non-PCOS cycles, numbers of retrieved oocytes and of all embryos that could be transferred, as well as rates of good-quality embryos, embryo implantations and clinical pregnancies, progressively increased with FORT. In PCOS patients, FORT were significantly lower in patients who achieved clinical pregnancy compared with those who did not (0.56 ± 0.21 versus 0.66 ± 0.29, P = 0.031). Fertilization and good-quality embryo rates were significantly higher with medium FORT than low and high FORT (P = 0.001 and P = 0.047, respectively). Medium FORT in PCOS patients and high FORT in non-PCOS patients may predict better outcomes for IVF/ICSI.In the present study, we aimed to assess the true accuracy of the follicular output rate (FORT) as a prognostic indicator of the response to FSH and reproductive competence after IVF/intracytoplasmic sperm injection (ICSI). A total of 1643 IVF/ICSI cycles, including 140 polycystic ovary syndrome (PCOS) patients who underwent ovarian stimulation, were studied. FORT was calculated as the ratio of the preovulatory follicle count (PFC) on the day of human chorionic gonadotrophin stimulation × 100/small antral follicle count (AFC; 3–10 mm in diameter) at baseline. Low, medium and high FORT groups were defined according to the tertile values. Among 1503 non-PCOS cycles, the numbers of retrieved oocytes and of all embryos that could be transferred, as well as the rates of good-quality embryos, embryo implantations and clinical pregnancies, progressively increased from the lower to higher FORT groups. In PCOS patients, FORT was significantly lower in the patients who achieved clinical pregnancy compared with those who did not (0.56 ± 0.21 versus 0.66 ± 0.29, P < 0.05). Fertilization and good-quality embryo rates were significantly higher in the medium FORT group compared with the low and high FORT groups. The data from the present study suggest that medium FORT values in PCOS patients and high FORT values in non-PCOS patients may predict better outcomes for IVF/ICSI.     

FIV conventionnelle versus ICSI sur une même cohorte ovocytaire : analyse de l’expérience française pour les BLEFCO

Assisted Reproductive Techniques (ART) separating oocytes in sibling oocytes treated either by conventional IVF or ICSI is called mid-IVF/ICSI. We sum up here 487 attempts of this kind from six French ART centers. The mid-IVF/ICSI technique was performed in 5.6% of cases. The fertilization rate by micro-injected oocytes was significantly higher (P < 0.01) than oocytes inseminated conventionally, 72.6% versus 53.4%. A failure of fertilization was observed only in mid-IVF in 21.6% of cases, which prevented a complete fertilization failure when we decided to propose to the couples concerned the mid-IVF/ICSI technique. Conversely, in 75.2% of cases, fertilization was found for the two batches of oocytes. The overall pregnancy rate has improved since the use of the mid-IVF/ICSI technique (33.1% versus 28.9%, P = 0.013) and the fertilization failures decreased (10.4% versus 14.3%, P = 0. 019). The pregnancy rate in only mid-IVF/ICSI cases is very high at 39.8% but for a selected population. The indications for mid-IVF/ICSI remain to be clarified especially with regard to male and idiopathic indications.     

Chromosome abnormality rates in human embryos obtained from in-vitro maturation and IVF treatment cycles

The aim of this retrospective study was to compare the incidence of chromosomal abnormality in embryos from in-vitro maturation (IVM) and IVF cycles. The copy numbers of chromosomes 13, 15, 16, 18, 21, 22, X and Y were assessed with fluorescence in-situ hybridization (FISH) in single blastomeres biopsied from cleavage stage embryos. Spare embryos that were not transferred or cryopreserved were also analysed in full. IVM and IVF groups comprised six and 30 couples, with mean ± SD embryos with FISH result of 8.0 ± 4.4 and 11.7 ± 3.8, respectively. The incidence of chromosomal abnormality per FISH result was similar in IVM and IVF embryos (58.7% versus 57.4%, respectively). When embryos were categorized based on maturation time of oocytes in IVM cycles, embryos derived from oocytes that matured 48 h after collection had a higher chromosomal abnormality rate compared with embryos derived from in-vivo matured oocytes and to embryos derived from oocytes that matured in the first 24 h after collection.     

Atosiban improves implantation and pregnancy rates in patients with repeated implantation failure

This prospective cohort study examined the effects of atosiban on uterine contraction, implantation rate (IR) and clinical pregnancy rate (CPR) in women undergoing IVF/embryo transfer. The study enrolled 71 women with repeated implantation failure (RIF; no pregnancies from an average of 4.8 previous embryo transfers with a mean of 12 top-quality embryos) undergoing IVF/embryo transfer using cryopreserved embryos. The total atosiban dose was 36.75 mg. The IR per transfer and CPR per cycle were 13.9% and 43.7%, respectively. Before atosiban, 14% of subjects had a high frequency of uterine contractions (?16 in 4 min). The frequency of uterine contractions was reduced after atosiban. This reduction of uterine contractions in all cycles was significant overall (from 6.0 to 2.6/4 min; P < 0.01), in cycles with ?16 uterine contractions/4 min at baseline (from 18.8 to 5.1; P < 0.01) and in cycles with <16 uterine contractions/4 min (from 3.9 to 2.2; P < 0.01). IR and CPR improved in all subjects, irrespective of baseline uterine contraction frequency. This is the first prospective study showing that atosiban may benefit subjects with RIF undergoing IVF/embryo transfer with cryopreserved embryos. One potential mechanism is the reduction in uterine contractility, but others may also contribute.Many women undergoing IVF/embryo transfer do not achieve the outcome that they wish for. In fact, IVF/embryo transfer repeatedly fails for a subgroup of patients. There are limited options available to help these patients with repeat implantation failure (RIF) to become pregnant. This study looks at one potential new treatment option for women who experience RIF. A drug called atosiban is already being used to delay premature labour by inhibiting contractions of the uterus. In this study, atosiban was given at the time of embryo transfer to women undergoing IVF/embryo transfer. Atosiban reduced the number of uterine contractions in these patients and also increased the implantation and pregnancy rates. The pregnancy rate went from zero to 43.7%. The beneficial effects of atosiban were observed not only in patients who had a high frequency of uterine contractions at baseline but also in those who had a low frequency. These findings suggest that atosiban may have other benefits in addition to its effect on contractions of the uterus. More studies are required to find out exactly how atosiban works and to increase the knowledge of its use in patients with RIF undergoing IVF/embryo transfer.     

L’apport de la vitrification dans l’efficience de la fécondation in vitro

This work aims to show, from data available in the literature and our own experience, how embryos’ vitrification change and/or improve the management of infertile couples. In all, 652 cycles of frozen-thawed embryo transfers (FET) following vitrification were prospectively included and compared with 1126 FETs from slow freezing (SF) method. Primary end points were the (i) survival rate (SR) (% of embryos with > 50% post-thaw intact blastomeres) and (ii) intact survival rate (ISR) (% of embryos with 100% post-thaw intact blastomeres). Secondary end point was the clinical pregnancy rate (CPR) defined as the presence of an intra uterine gestational sac with positive foetal heart beat. In all, 1097 and 2408 embryos have been thawed following vitrification and SF, respectively. We observed a highly significant increase of SR and ISR respectively when thawing concerned vitrified embryos rather than those from SF method (97.0% vs. 72.7%, P < 10⁻⁴; 91.5% vs. 49.8%, P < 10⁻⁴). Furthermore, CPR were of 26.5% (73/652) and of 18.1% (204/1126) following FETs performed after vitrification or SF and thawing (P = 0.0002), respectively. At the blastocyst stage, ISR was significantly improved following vitrification compared to SF (94.5% vs. 21.4%, P < 10⁻⁴). In the study period, vitrification (i) reduced the mean number of fresh transferred embryos (1.5 vs. 1.6; P = 0.08) and (ii) increased the rate of FETs at the blastocyst stage when compared with the control period (18.1% vs 2.5%., P < 10⁻⁴). Embryo vitrification preserves all embryos from an ART cycle because of its excellent results regarding ISR at all stages of embryo development. This procedure allows a significant increase of pregnancy rates after thawing. In addition, there is a trend for increasing ART cycles performed using extended culture embryo and vitrification. The expected improvement of the cumulative birth rate at the blastocyst stage following vitrification remains to be demonstrated in a prospective randomized study.     

Ovarian reserve and PGD treatment outcome in women with myotonic dystrophy

Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults. There are conflicting reports about its effect on female fertility. This study investigated ovarian reserve and IVF–preimplantation genetic diagnosis (PGD) outcome in women with DM1. A total of 21 women undergoing PGD for DM1 were compared with 21 age- and body mass index-matched women undergoing PGD for other diseases. Ovarian reserve markers, response to stimulation, embryo quality and clinical pregnancy and live birth rates were compared. Day-3 FSH concentration was higher, while anti-Müllerian hormone concentration and antral follicle count were lower in the DM1 group (median, range: 6.9 (1.8–11.3) versus 5.7 (1.5–10.7) IU/l; 0.9 (0.17–5.96) versus 2.68 (0.5–9.1) ng/ml; and 13 (0–63) versus 23 (8–40) follicles, respectively, all P < 0.05). Total FSH dose was higher (5200 versus 2250 IU, P = 0.004), while the numbers of oocytes retrieved (10 versus 16, P < 0.04) and metaphase-II oocytes (9 versus 12, P < 0.03) were lower in the DM1 group. The number of cycles with top-quality embryos and the clinical pregnancy rate were lower in the DM1 group. In conclusion, there is evidence of diminished ovarian reserve and less favourable IVF–PGD outcome in women with DM1.Myotonic Dystrophy (DM) is the most common form of muscular dystrophy in adults. There is evidence of subfertility in males affected with the disease but conflicting reports about the effect of the disease on female fertility. The aim of our study was to investigate ovarian reserve and IVF–PGD results in women with DM. Twenty-one women undergoing preimplantation genetic diagnosis (PGD) treatment for DM were compared to 21 age- and BMI matched women undergoing PGD treatment for other diseases. The two groups were compared for antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) levels (the best known markers of ovarian reserve and fertility potential), ovarian response, embryo quality and pregnancy and live birth rates. AFC and the AMH levels were statistically significant lower in the DM group. Total medication dose needed for ovarian stimulation was higher, the number of oocytes and mature oocytes retrieved, and the number of cycles with top quality embryos were lower in the DM group compared to the controls. In conclusion, there is evidence of diminished ovarian reserve, and less favorable IVF-PGD outcome in women with DM. Therefore, we recommend advising these women about the possibility of early decreasing ovarian function in order to prevent any delay in reproductive planning.     

Follicle recruitment determines IVF productivity rate via the number of embryos frozen and subsequent transfers

IVF productivity rate is an index defined as the sum of all live births from either fresh or frozen embryo transfers arising from a single oocyte collection. This retrospective analysis over 9 continuous years used this index to understand the potential impact on pregnancy rates of milder stimulation regimens with associated reduced egg numbers. The productivity rate per collection increased in a linear and significant rate as more oocytes were recovered, more embryos frozen and more frozen embryo transfers contributed to pregnancy. This observation was true for women aged <35 years and less so for women aged 35–39 years but not for women aged 40 years and older. The contribution of frozen embryo transfer to the productivity rate rose in a linear manner, reaching over 40% of all live births with nine oocytes. The number of live births per oocyte, pronuclear embryos and thawed embryos decreased significantly but the number of live births per embryo transferred (fresh or frozen) rose with rising oocyte numbers, reflecting increasing opportunity for embryo selection. This study suggests that optimal benefits with minimal risks are gained from a model that includes both fresh and frozen transfers under stimulation generating between 8 and 12 eggs.Most of the costs and risks associated with an IVF cycle occur during the stimulation, egg collection and subsequent transfer of fresh embryos and ignore or treat separately the outcome from any subsequent frozen embryo transfers. We have used the term ‘productivity rate’ (or cumulative pregnancy rate per collection cycle) that includes outcomes from both fresh and frozen transfers as a tool to explore the impact of oocyte numbers on the ultimate chance of pregnancy. While the pregnancy rate for individual fresh and frozen transfers were largely unrelated to oocyte numbers, the cumulative chance of pregnancy rose significantly with the number of oocytes recovered. This was due to the increasing contribution of frozen embryo transfers to the overall chance of pregnancy producing more than half of all pregnancies above five oocytes. While the fertilization rate and embryo quality was independent of egg numbers, increasingly more embryos needed to be used to generate sufficient good-quality embryos for transfers as the egg numbers rose. The study found that 8–12 oocytes provided the highest cumulative chance of pregnancy with the least risk of either failed fertilization or ovarian hyperstimulation syndrome and this range could be used as a target number for individualized stimulation regimens.     

Nitric oxide as an early marker of human embryo metabolic cleavage in ART using fresh or thawed oocytes

ObjectiveTo study a possible role of nitric oxide (NO) as a marker of development in the early phases of human embryo cleavage during assisted reproduction.Study design179 women having ART were included. 123 women used fresh oocytes and 56 oocyte thawing cycles in the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova, between July 2005 and June 2006; 57 patients had IVF and 122 patients had ICSI. NO concentrations in IVF or ICSI embryo culture media were assessed by monitoring levels of NO stable oxidation products (nitrites/nitrates). Analysis of embryo quality was performed. Student’s t-test or Mann–Whitney and logistic regression model tests were applied to the data.ResultsIn patients using fresh oocytes, there were greater NO production in embryos derived from ICSI than from IVF after 52 h of culture (38.64 μmol/L vs 11.2 μmol/L, p < 0.05). No correlation with embryo quality was observed. Embryos derived from fresh oocytes produce more NO than embryos from thawed oocytes both after 48 and 52 h of culture (16.12 μmol/L vs 6.83 μmol/L and 25.93 μmol/L vs 2.98 μmol/L respectively, p < 0.05).Conclusion(s)NO in embryo culture media is not a metabolic cleavage marker or a marker of embryo quality in ART. However, it could be an important parameter in the investigation of metabolism in frozen/thawed oocytes.     

Impact of an educational intervention and insurance coverage on patients’ preferences to transfer multiple embryos

Multiple gestations resulting from IVF continue to be a major problem associated with maternal/neonatal morbidity and mortality including preterm labour/delivery, pre-eclampsia and post-partum haemorrhage. A prospective survey at a university IVF clinic evaluated the effect of education and insurance coverage on patients’ preferences for single-embryo transfer (SET) versus double-embryo transfer (DET). Patients undergoing IVF treatment from September 2008 to October 2009 were included. The main outcome measure was patients’ preference of SET versus DET. Patients were sent an educational handout describing maternal and fetal risks of twin gestation. A total of 163 patients (32.6% response rate) returned the pre- and post-education surveys regarding preferences for SET versus DET based on three different IVF insurance coverage scenarios (no coverage, two cycles covered and unlimited coverage). There were statistically significant differences in the preference for SET before and after education across all insurance scenarios (scenario 1, 42.0% versus 61.1%; scenario 2, 50.6% versus 71.0%; and scenario 3, 61.7% versus 79.6%; P < 0.001 for all scenarios). Before education, patients preferred SET more in the unlimited coverage scenario (61.7%) versus no coverage (42.0%; P < 0.001). An educational handout and increasing the amount of insurance coverage significantly increased a patient’s preference for SET.Multiple gestations resulting from IVF continue to be a major problem. Twin gestation increases the risk of pregnancy for the mother as well as the newborn. One strategy used to decrease the incidence of twins from IVF is transferring a single embryo. A prospective survey study was performed at a university IVF clinic. Our objective was to evaluate the effect of education and insurance coverage on a patient’s preference for single- versus double-embryo transfer. The population included patients undergoing IVF treatment from September 2008 to October 2009. The main outcome measure was a patient’s preference of single- versus double-embryo transfer. A total of 162 patients were surveyed before and after education regarding the maternal and fetal risks of a twin gestation on their preferences for a double- versus single-embryo transfer. Patients were given three different scenarios regarding IVF insurance coverage including either no IVF insurance coverage, limited IVF insurance coverage or unlimited IVF insurance coverage. There were statistically significant differences in the preference for a single-embryo transfer before and after education across all insurance scenarios (P < 0.001). Patients preferred single-embryo transfer more in the unlimited coverage scenario versus the no coverage (P < 0.001). An educational handout and increasing the amount of insurance coverage significantly increased a patient’s preference for single embryo transfer.     

Long-term androgen priming by use of dehydroepiandrosterone (DHEA) improves IVF outcome in poor-responder patients. A randomized controlled study

IntroductionSuccess with COH depends on the ability to recruit adequate numbers of follicles. Unfortunately, some patients produce too few follicles with COH and are classified as poor responders. Over the years, numerous techniques and therapies have been developed in an effort to help the poor responder, but few have met with success. Recently attempts of ovarian androgen priming have been developed on the basis that temporary exposure of follicles to increased levels of androgens may augment their responsiveness to FSH. Long-term DHEA exposure can induce histological and sonographic changes in normal ovaries similar to PCOS. This effect is cumulative as more of the antral follicles become exposed to treatment.ObjectiveThe aim of this study was to compare the effect of DHEA supplementation on IVF treatment outcomes among a cohort of women with known decreased ovarian reserve using a short protocol.DesignIt is a randomized controlled study.Materials and methodsBetween July 2008 and April 2012, 133 patients with a prior poor response to ovarian stimulation in IVF were selected to undergo an IVF cycle. The cases were divided without prejudice into 2 groups; (1) study group (DHEA group); in which the patient began taking 25 mg of DHEA orally, three times a day, for at least 12 weeks before starting COH, (2) control group; in which the patient started COH without DHEA priming.ResultsThe study group had statistically significant higher numbers of retrieved oocytes (5.9 ± 3.6) compared to the control group (3.5 ± 2.9) – P < 0.001. Also, the study group had a statistically significant lower cancellation rate (13.4%) and a higher number of embryos transferred (2.8 ± 0.9) compared to the control group (28.8% and 1.7 ± 1.1, respectively) – P < 0.01 & <0.001, respectively. Although the pregnancy rate (per embryo transfer) was higher in the study group (24.1%) compared to the control group (21.3%), no statistically significant difference was observed. However, if we calculate pregnancy rate per cycle, it was significantly higher in the study group (20.9%) compared to (15.2%) in the control group – P < 0.05.ConclusionAccording to our findings, long-term androgen priming by use of DHEA improves IVF outcome in poor responder patients. Additional, larger studies, using different protocols are needed to reinforce our findings.