Can You Ever Collect Too Many Oocytes?
Can You Ever Collect Too Many Oocytes?
Study Question Does the chance of pregnancy keep improving with increasing number of oocytes, or can you collect too many?
Summary Answer Clinical pregnancy (CP) and live birth (LB) rates per embryo transfer varied from 10.2 and 9.2% following one oocyte collected to 37.7 and 31.3% when >16 oocytes were collected. Regression modelling indicated success rates increased or at least stayed the same with number of oocytes collected.
What Is Known Already It has been suggested that if >15 oocytes are collected, the success rate for fresh embryo transfers decreases. As this is counterintuitive, as more oocytes should result in more embryos, with a better choice of quality embryos, we decided to analyse the recent experience in a busy IVF unit.
Study Design, Size Duration A retrospective analysis of clinical pregnancy and live birth outcome, with respect to number of oocytes collected at Monash IVF for the 2-year period between August 2010 and July 2012, where patients under the age of 45 years underwent a fresh embryo transfer. This included 7697 stimulated cycles for IVF and ICSI.
Participant/Materials, Setting, Methods Statistical analysis involved data tables and graphs comparing oocyte number with outcome. Results of women who had their first oocyte collection with an embryo transfer within the reference period were analysed by logistic regression analysis including other covariates that might influence pregnancy outcome. Analysis was also carried out of all the 7679 oocyte collections undertaken, resulting in fresh embryo transfers by generalized estimating equations to allow for the within subject correlation in outcomes for repeated treatments.
Main Results and the Role of Chance The number of oocytes collected varied from 1 to 48. Clinical pregnancy and live birth rates per embryo transfer varied from 10.2 and 9.2% when only one oocyte was collected to 37.7 and 31.3% when >16 oocytes were collected. Regression modelling indicated success rates increased or at least stayed the same or with the number of oocytes collected. The percentage of women with embryos cryopreserved increased from under 20% with <4 oocytes collected to over 70% with >16 oocytes collected. There was a slight increase (from 18 to 22%) in oocyte immaturity and a more marked increase (from 0 to 3%) in cancelling fresh transfers to prevent Ovarian Hyperstimulation Syndrome (OHSS) with increase in number of oocytes collected above 16. The results of this study suggest that you cannot collect too many oocytes as both clinical pregnancy and live birth rates do not decrease with high numbers of oocytes collected. However, once >15 oocytes are collected, everything gets quite uncertain.
Limitations, Reasons for Caution As the data become sparse above 15 oocytes, we could not demonstrate a significant increase in pregnancy rates above this number. Larger studies would be required to answer the question whether there is a plateau, or rates continue to increase. The negative of aggressive stimulation to produce many oocytes is that the risk of OHSS increases, and this is the most serious complication of ovarian stimulation.
Study Funding/Completing of Interest(S) No funding was required. There is no conflict of interest, except that G.K., V.M. and C.M. are shareholders in Monash IVF Pty Ltd.
The first successful IVF live births were a result of natural cycles (Steptoe and Edwards, 1978; Lopata et al., 1980). However, the success rate of these cycles was low. This led to the utilization of stimulated cycles, which were pioneered with the use of Clomiphene Citrate (Trounson et al., 1981), and later with FSH (Jones et al., 1982). Controlled ovarian hyperstimulation (COH) became routine and there have been many modifications of treatment since, including the use of highly purified FSH and the use of GnRH agonists and later GnRH antagonists to inhibit ovulation.
Along with their success, stimulated cycles led to other problems, including ovarian hyper-stimulation syndrome (OHSS). It has also been suggested that the high level of estrogen in COH cycles may be detrimental to oocyte quality as well as to the endometrium. Higher doses of hormones used in stimulated cycles can produce higher yields of oocytes but it has been reported that excessive stimulation and high levels of estrogen, may compromise results. There have been several previous studies suggesting that beyond a certain number of oocytes collected the pregnancy rate in the stimulated cycle with fresh embryo transfer, starts to decline. The optimum number of oocytes varied from 13 (van der Gaast et al., 2006), 15 to 20 (Sunkara et al., 2011), or as wide a range as 6 to 15 (Ji et al., 2013), whilst a study by Kok and colleagues (Kok et al., 2006) suggested that although high responders had a higher percentage of immature oocytes, the pregnancy outcome was not impaired.
The suggestion that one can have 'too many oocytes?' is anti-intuitive, as if there are more oocytes available for fertilization, there should be a higher number of embryos produced, giving greater choice for embryo transfer and a better outcome.
These studies include cycles using older stimulation protocols, and the purpose of the current study was to investigate if their conclusions remain true for more modern stimulation protocols and with the evolution of delayed transfer at the blastocyst stage.
We therefore carried out a retrospective analysis of clinical pregnancy and live birth outcome, with respect to number of oocytes collected.
Abstract and Introduction
Abstract
Study Question Does the chance of pregnancy keep improving with increasing number of oocytes, or can you collect too many?
Summary Answer Clinical pregnancy (CP) and live birth (LB) rates per embryo transfer varied from 10.2 and 9.2% following one oocyte collected to 37.7 and 31.3% when >16 oocytes were collected. Regression modelling indicated success rates increased or at least stayed the same with number of oocytes collected.
What Is Known Already It has been suggested that if >15 oocytes are collected, the success rate for fresh embryo transfers decreases. As this is counterintuitive, as more oocytes should result in more embryos, with a better choice of quality embryos, we decided to analyse the recent experience in a busy IVF unit.
Study Design, Size Duration A retrospective analysis of clinical pregnancy and live birth outcome, with respect to number of oocytes collected at Monash IVF for the 2-year period between August 2010 and July 2012, where patients under the age of 45 years underwent a fresh embryo transfer. This included 7697 stimulated cycles for IVF and ICSI.
Participant/Materials, Setting, Methods Statistical analysis involved data tables and graphs comparing oocyte number with outcome. Results of women who had their first oocyte collection with an embryo transfer within the reference period were analysed by logistic regression analysis including other covariates that might influence pregnancy outcome. Analysis was also carried out of all the 7679 oocyte collections undertaken, resulting in fresh embryo transfers by generalized estimating equations to allow for the within subject correlation in outcomes for repeated treatments.
Main Results and the Role of Chance The number of oocytes collected varied from 1 to 48. Clinical pregnancy and live birth rates per embryo transfer varied from 10.2 and 9.2% when only one oocyte was collected to 37.7 and 31.3% when >16 oocytes were collected. Regression modelling indicated success rates increased or at least stayed the same or with the number of oocytes collected. The percentage of women with embryos cryopreserved increased from under 20% with <4 oocytes collected to over 70% with >16 oocytes collected. There was a slight increase (from 18 to 22%) in oocyte immaturity and a more marked increase (from 0 to 3%) in cancelling fresh transfers to prevent Ovarian Hyperstimulation Syndrome (OHSS) with increase in number of oocytes collected above 16. The results of this study suggest that you cannot collect too many oocytes as both clinical pregnancy and live birth rates do not decrease with high numbers of oocytes collected. However, once >15 oocytes are collected, everything gets quite uncertain.
Limitations, Reasons for Caution As the data become sparse above 15 oocytes, we could not demonstrate a significant increase in pregnancy rates above this number. Larger studies would be required to answer the question whether there is a plateau, or rates continue to increase. The negative of aggressive stimulation to produce many oocytes is that the risk of OHSS increases, and this is the most serious complication of ovarian stimulation.
Study Funding/Completing of Interest(S) No funding was required. There is no conflict of interest, except that G.K., V.M. and C.M. are shareholders in Monash IVF Pty Ltd.
Introduction
The first successful IVF live births were a result of natural cycles (Steptoe and Edwards, 1978; Lopata et al., 1980). However, the success rate of these cycles was low. This led to the utilization of stimulated cycles, which were pioneered with the use of Clomiphene Citrate (Trounson et al., 1981), and later with FSH (Jones et al., 1982). Controlled ovarian hyperstimulation (COH) became routine and there have been many modifications of treatment since, including the use of highly purified FSH and the use of GnRH agonists and later GnRH antagonists to inhibit ovulation.
Along with their success, stimulated cycles led to other problems, including ovarian hyper-stimulation syndrome (OHSS). It has also been suggested that the high level of estrogen in COH cycles may be detrimental to oocyte quality as well as to the endometrium. Higher doses of hormones used in stimulated cycles can produce higher yields of oocytes but it has been reported that excessive stimulation and high levels of estrogen, may compromise results. There have been several previous studies suggesting that beyond a certain number of oocytes collected the pregnancy rate in the stimulated cycle with fresh embryo transfer, starts to decline. The optimum number of oocytes varied from 13 (van der Gaast et al., 2006), 15 to 20 (Sunkara et al., 2011), or as wide a range as 6 to 15 (Ji et al., 2013), whilst a study by Kok and colleagues (Kok et al., 2006) suggested that although high responders had a higher percentage of immature oocytes, the pregnancy outcome was not impaired.
The suggestion that one can have 'too many oocytes?' is anti-intuitive, as if there are more oocytes available for fertilization, there should be a higher number of embryos produced, giving greater choice for embryo transfer and a better outcome.
These studies include cycles using older stimulation protocols, and the purpose of the current study was to investigate if their conclusions remain true for more modern stimulation protocols and with the evolution of delayed transfer at the blastocyst stage.
We therefore carried out a retrospective analysis of clinical pregnancy and live birth outcome, with respect to number of oocytes collected.
