transvaginal ultrasound - guided oocyte pick - up ( opu ) for assisted reproductive technology ( art ) treatment was first reported in 1985 ( 1 ) . since then
, this technique has been rapidly widespread throughout the world , as a replacement for laparoscopic oocyte retrieval .
currently , the ovarian stimulation protocol for art treatment is changing from hyperstimulation to mild or minimal stimulation protocol by minimizing the dose of parenteral follicle stimulation or shifting to oral medicine ( 2 ) . as a result , the number of follicles punctured and oocytes retrieved during opu has decreased . in our clinic , the average number of retrieved oocytes among patients aged 3740 years has been reported as 3.7 ( 3 ) , and no anesthesia ( either local or general ) is used during opu in more than half of our patients . however , even when only a single follicle is punctured , oocyte retrieval can be painful .
therefore a method for reducing pain during oocyte retrieval is needed , particularly for cases where anesthesia is not used . recently , a newly designed needle for opu was launched with the aim of reducing pain during opu ( 4 ) .
the tip of the needle ( i.e. the last 50 mm , the part that penetrates into the tissues ) is thinner than standard , with the remainder of the needle having a larger diameter .
an initial study showed that overall pain experienced during opu with the reduced needle was significantly lower than that with the standard needle ( 4 ) .
however , there were limitations with that study : several follicles were aspirated during each procedure , and local anesthesia was administrated . for studies investigating the effect of a new needle ,
it is important to ensure that number of aspirated follicles is the same in both study groups and that perceived pain is not masked by analgesic treatment .
therefore , in the present study , an attempt was made to evaluate the effect of reduced needle on pain and vaginal bleeding associated with single - follicle opu in patients who did not receive any analgesic treatment .
from may through november 2013 , 100 patients were screened for the study and 75 were enrolled ( figure 1 ) .
twenty - five screened patients could not be enrolled in this study because they ovulated before planned oocyte aspiration .
therefore , there were no protocol violations and all analyses were performed according to the intention to treat .
ovarian follicles were matured by either a natural cycle or a clomiphene citrate cycle . signed informed consent
was obtained from all patients , and this study was approved by the institutional board of the sugiyama clinic .
flow chart showing patients progression through the study the study was registered with the umin clinical trials registry , study number umin000014 800 .
patients were randomized on the day of oocyte retrieval into either the reduced needle ( rn ) group or the standard needle ( sn ) group , with a 1:1 allocation ratio .
the needle used for the procedure was not known to the patient but for practical reasons it was known to the treating physician .
all opu procedures were performed trans - vaginally , by a single physician , with ultra - sonography to guide the needle .
patients were randomly assigned to one of the two groups on the day of oocyte aspiration . in each case , a single follicle with a mean diameter of > 17 mm was aspirated , using either a reduced needle with a 17 gauge body and a 20 gauge tip ( sense , vitrolife , sweden ; rn group ) or a standard 19 gauge needle ( uniever oocyte aspiration needle , japan ; sn group ) .
all needles were connected to a syringe ( via a luer connection ) for manual suction , meaning that the aspiration pressure could be controlled as needed .
if an oocyte could not be retrieved following puncture , follicle flushing was performed up to 5 times .
pain was rated by each patient immediately after the opu by means of a visual analogue scale ( vas ) , comprising a vertical line from 0 cm ( no pain ) to 10 cm ( unbearable pain ) ( 5 ) .
all patients were asked by the same medical doctor to mark the vas with their rating of the overall pain for the whole procedure . the pain perceived by patients
30 min after the procedure , captured in the same way as overall pain , was a secondary endpoint .
bleeding from the vaginal wall ( at the point of needle penetration ) was also evaluated after opu .
 bleeding  was defined as continuous signs of bleeding even after the application of direct compression for 30 s , and  no bleeding  defined as cessation of blood loss after direct compression .
the in vitro fertilization ( ivf ) procedure used in the present study has been described previously ( 6 ) .
the retrieved oocyte was fertilized by conventional insemination or intracytoplasmic sperm injection ( icsi ) three to five hours after follicle aspiration .
the presence of two pronuclei with extrusion of the second polar body was taken as the evidence of successful fertilization .
embryos were evaluated microscopically before transfer , and those with more than seven blastomeres and less than 10% fragmentation were classified as morphologically good - quality embryos ( mges ) ( 7 ) .
embryos were placed transcervically into the uterus using a soft et catheter ( kitazato , japan ) ( 8) .
pregnancy was recognized when the development of a gestational sac was evident from transvaginal ultrasound on the 21st day after embryo transfer .
the level of pain associated with the procedures is higher when it is performed without anesthesia , and the average vas score for the primary endpoint  overall pain experience  was anticipated to be 5.0 cm with the standard needle .
the reduced needle was expected to reduce the vas pain score by 1.2 cm ( 24% ) , a clinically significant difference .
forty - four patients would be needed in each study group to demonstrate this difference with 80% power and a significance level of 0.05 ( two - tailed tests ) .
fisher s exact test was used to analyze dichotomous data and student s t - test and wilcoxon test when normality distribution was rejected were used for continuous variables
from may through november 2013 , 100 patients were screened for the study and 75 were enrolled ( figure 1 ) .
twenty - five screened patients could not be enrolled in this study because they ovulated before planned oocyte aspiration .
therefore , there were no protocol violations and all analyses were performed according to the intention to treat .
ovarian follicles were matured by either a natural cycle or a clomiphene citrate cycle . signed informed consent
was obtained from all patients , and this study was approved by the institutional board of the sugiyama clinic .
flow chart showing patients progression through the study the study was registered with the umin clinical trials registry , study number umin000014 800 .
patients were randomized on the day of oocyte retrieval into either the reduced needle ( rn ) group or the standard needle ( sn ) group , with a 1:1 allocation ratio .
the needle used for the procedure was not known to the patient but for practical reasons it was known to the treating physician .
all opu procedures were performed trans - vaginally , by a single physician , with ultra - sonography to guide the needle .
patients were randomly assigned to one of the two groups on the day of oocyte aspiration . in each case , a single follicle with a mean diameter of > 17 mm was aspirated , using either a reduced needle with a 17 gauge body and a 20 gauge tip ( sense , vitrolife , sweden ; rn group ) or a standard 19 gauge needle ( uniever oocyte aspiration needle , japan ; sn group ) .
all needles were connected to a syringe ( via a luer connection ) for manual suction , meaning that the aspiration pressure could be controlled as needed .
if an oocyte could not be retrieved following puncture , follicle flushing was performed up to 5 times .
from may through november 2013 , 100 patients were screened for the study and 75 were enrolled ( figure 1 ) .
twenty - five screened patients could not be enrolled in this study because they ovulated before planned oocyte aspiration .
therefore , there were no protocol violations and all analyses were performed according to the intention to treat .
ovarian follicles were matured by either a natural cycle or a clomiphene citrate cycle . signed informed consent
was obtained from all patients , and this study was approved by the institutional board of the sugiyama clinic .
flow chart showing patients progression through the study the study was registered with the umin clinical trials registry , study number umin000014 800 .
patients were randomized on the day of oocyte retrieval into either the reduced needle ( rn ) group or the standard needle ( sn ) group , with a 1:1 allocation ratio .
the needle used for the procedure was not known to the patient but for practical reasons it was known to the treating physician .
all opu procedures were performed trans - vaginally , by a single physician , with ultra - sonography to guide the needle .
patients were randomly assigned to one of the two groups on the day of oocyte aspiration . in each case , a single follicle with a mean diameter of > 17 mm was aspirated , using either a reduced needle with a 17 gauge body and a 20 gauge tip ( sense , vitrolife , sweden ; rn group ) or a standard 19 gauge needle ( uniever oocyte aspiration needle , japan ; sn group ) .
all needles were connected to a syringe ( via a luer connection ) for manual suction , meaning that the aspiration pressure could be controlled as needed .
if an oocyte could not be retrieved following puncture , follicle flushing was performed up to 5 times .
pain was rated by each patient immediately after the opu by means of a visual analogue scale ( vas ) , comprising a vertical line from 0 cm ( no pain ) to 10 cm ( unbearable pain ) ( 5 ) .
all patients were asked by the same medical doctor to mark the vas with their rating of the overall pain for the whole procedure . the pain perceived by patients
30 min after the procedure , captured in the same way as overall pain , was a secondary endpoint .
bleeding from the vaginal wall ( at the point of needle penetration ) was also evaluated after opu .
 bleeding  was defined as continuous signs of bleeding even after the application of direct compression for 30 s , and  no bleeding  defined as cessation of blood loss after direct compression .
the in vitro fertilization ( ivf ) procedure used in the present study has been described previously ( 6 ) .
the retrieved oocyte was fertilized by conventional insemination or intracytoplasmic sperm injection ( icsi ) three to five hours after follicle aspiration .
the presence of two pronuclei with extrusion of the second polar body was taken as the evidence of successful fertilization .
embryos were evaluated microscopically before transfer , and those with more than seven blastomeres and less than 10% fragmentation were classified as morphologically good - quality embryos ( mges ) ( 7 ) .
embryos were placed transcervically into the uterus using a soft et catheter ( kitazato , japan ) ( 8) .
pregnancy was recognized when the development of a gestational sac was evident from transvaginal ultrasound on the 21st day after embryo transfer .
the level of pain associated with the procedures is higher when it is performed without anesthesia , and the average vas score for the primary endpoint  overall pain experience  was anticipated to be 5.0 cm with the standard needle .
the reduced needle was expected to reduce the vas pain score by 1.2 cm ( 24% ) , a clinically significant difference .
forty - four patients would be needed in each study group to demonstrate this difference with 80% power and a significance level of 0.05 ( two - tailed tests ) .
fisher s exact test was used to analyze dichotomous data and student s t - test and wilcoxon test when normality distribution was rejected were used for continuous variables
pain was rated by each patient immediately after the opu by means of a visual analogue scale ( vas ) , comprising a vertical line from 0 cm ( no pain ) to 10 cm ( unbearable pain ) ( 5 ) .
all patients were asked by the same medical doctor to mark the vas with their rating of the overall pain for the whole procedure .
the pain perceived by patients 30 min after the procedure , captured in the same way as overall pain , was a secondary endpoint .
bleeding from the vaginal wall ( at the point of needle penetration ) was also evaluated after opu .
 bleeding  was defined as continuous signs of bleeding even after the application of direct compression for 30 s , and  no bleeding  defined as cessation of blood loss after direct compression .
the in vitro fertilization ( ivf ) procedure used in the present study has been described previously ( 6 ) .
the retrieved oocyte was fertilized by conventional insemination or intracytoplasmic sperm injection ( icsi ) three to five hours after follicle aspiration .
the presence of two pronuclei with extrusion of the second polar body was taken as the evidence of successful fertilization .
embryos were evaluated microscopically before transfer , and those with more than seven blastomeres and less than 10% fragmentation were classified as morphologically good - quality embryos ( mges ) ( 7 ) .
embryos were placed transcervically into the uterus using a soft et catheter ( kitazato , japan ) ( 8) .
pregnancy was recognized when the development of a gestational sac was evident from transvaginal ultrasound on the 21st day after embryo transfer .
the level of pain associated with the procedures is higher when it is performed without anesthesia , and the average vas score for the primary endpoint  overall pain experience  was anticipated to be 5.0 cm with the standard needle .
the reduced needle was expected to reduce the vas pain score by 1.2 cm ( 24% ) , a clinically significant difference .
forty - four patients would be needed in each study group to demonstrate this difference with 80% power and a significance level of 0.05 ( two - tailed tests ) .
fisher s exact test was used to analyze dichotomous data and student s t - test and wilcoxon test when normality distribution was rejected were used for continuous variables
next , they underwent opu with either the rn or the sn ( figure 1 )
. the number of patients enrolled was lower than estimated in the sample size calculation .
patients baseline characteristics and data relating to the opu procedure are summarized in table 1 .
the average age in the rn group was 40.83.9 years , compared with 40.33.6 years in the sn group .
the mean number of retrieved oocytes was 0.970.16 in the rn group and 0.970.16 in the sn group , while the percentages of mature oocytes were 86.5% and 91.8% in the two groups , respectively .
overall , there were no significant differences between the two groups in baseline characteristics or opu procedure data .
baseline characteristics and oocyte pick - up ( opu ) procedure data in the reduced needle ( rn ) and standard needle ( sn ) groups meansd ; ns : not significant there was no significant difference in fertilization rate between the rn group and sn group ( table 2 ) .
the pregnancy rate was numerically higher in the rn group ( 33.3% vs. 16.6% ) , although this difference did not reach statistical significance ( table 2 ) .
assisted reproductive technology ( art ) outcomes in the reduced needle ( rn ) and standard needle ( sn ) groups mges : morphologically good - quality embryos ; ns : not significant the results relating to pain are shown in table 3 .
the mean vas score for overall pain experienced during opu was 3.22.0 cm in the rn group , significantly lower than the one in the sn group 4.92.2 ( p<0.01 ) .
there was no significant difference in pain experienced 30 min after opu between - groups .
the frequency of bleeding from the vaginal wall after opu was reduced by 26.3% in the rn group compared with the sn group ( p<0.05 ; table 3 ) .
pain and frequency of bleeding in the reduced needle ( rn ) and standard needle ( sn ) groups meansd ; ns : not significant
another strategy is to use a thinner needle for the procedure . in the present study ,
overall pain during oocyte aspiration was significantly lower with a newly designed  reduced  needle with a thinner tip , in comparison with the standard needle .
no negative effects were found with the rn group in relation to oocyte fertilization , embryo morphology , or pregnancy rate .
it is difficult to evaluate pain experience during opu , because many factors can have an influence such as fear of pain , anxiety , physician s skill , operation time and technical factors including needle diameter and sharpness during opu .
analgesia is another potential factor , although that was not the case here because analgesic was not used . in a previous study of the rn ,
all patients received local anesthetic using paracetamol and had paracercivcal block with lidocaine ( 4 ) .
moreover , all patients received ovarian stimulation , meaning that several follicles were aspirated and the total opu time was longer than the time in the present study . under such conditions , it may be difficult to evaluate accurately the effect of the rn on pain . in the present study
, it was hoped that the effect of the rn might be more obvious because patients had only one follicle aspirated and no analgesic drugs were used .
in addition , to avoid possible bias related to multiple operators , all opus were performed by a single physician in the present study .
consequently , a reduction in vas pain score was observed from 4.9 to 3.2 cm , a much larger relative reduction than in the previous study where corresponding vas scores were 2.6 and 2.1 cm .
too much reduction of the needle diameter risks damaging the oocytes , although few studies have investigated this issue . with bovine oocytes , it has been demonstrated that both the diameter and bevel of the needle , as well as the aspiration vacuum , affect the recovery rate and developmental competence of oocyte ( 10 , 11 ) .
previous investigation of the rn used in the present study concluded that human oocytes are unaffected by using a needle with a 20 gauge tip and an aspiration pressure of 90120 mmhg ( 4 ) .
previously , a prototype needle similar to the rn investigated in this study was created . like
the needle reported here , the prototype had a luer connection , a 17 gauge body and a 20 gauge tip .
the oocyte recovery rate with this needle was comparable with that of a conventional needle .
however , approximately 50% of retrieved oocytes had degenerated and it was concluded that the prototype needle was harmful for oocytes ( data not shown ) .
this may be attributable to the way in which the prototype was made : where the two constituent needles was joined , the inner wall would not have been smooth and the flow of fluid passed this point would potentially have been turbulent .
since the study was performed by a single physician on single - follicle oocyte retrievals with no analgesic treatment , patient perceived pain and physician perceived bleeding could be appropriately studied . still , one potential limitation of the current study was the relatively small number of the patients recruited .
however , statistical analysis demonstrated that the study had sufficient power to detect an important difference .
it was also thought that the patients would like to change our clinical practice quickly , taking into account the outcome of the study .
another potential limitation of the study was that the type of needle was not blind to the physician .
however , since the technique and average opu time were the same in both groups , it is unlikely that this would impact the results .
this needle is not only useful for single - follicle oocyte retrievals in patients with no analgesic treatment but also more broadly in patients with fear of aspiration and those with a low threshold for pain .
it will also be useful for patients with a history of bleeding and patients undergoing fertility preservation in conjunction with blood cancer treatment such as leukemia or lymphoma .
patient perceived pain during single - follicle oocyte retrieval without analgesic was significantly lower with the newly designed aspiration needle with a thin tip than with a standard needle . in addition , post - procedural bleeding from the vaginal wall was lower with the rn .
 background : the purpose of this study was to evaluate the effect of needle type on pain and bleeding during oocyte pick - up ( opu).methods : from may through november 2013 , patients undergoing opu from a single follicle without any analgesic treatment were including this study . 
 eligible patients ( n=75 ) were randomized 1:1 to undergo the procedure with either a reduced needle ( 17 gauge body , 20 gauge tip ; rn group ) or a standard needle ( 19 gauge ; sn group ) . 
 overall pain was assessed by patients using a visual analogue scale ( vas ) , and vaginal bleeding after the procedure was recorded . 
 fisher exact , t - test or wilcoxon test were used , and p<0.05 was considered to be statistically significant.results:the percentage of mature oocytes was 86.5% in the rn group and 91.7% in the sn group . 
 pain during opu was significantly lower in the rn group than in the sn group ( mean vas scoresd : 3.22.0 cm vs. 4.92.2 cm , p<0.01 ; meansd ) . 
 the frequency of vaginal bleeding was also significantly lower in the sn group ( 26.3% vs. 48.6% ; p<0.05 ) . 
 the frequency of bleeding in the rn group was also significantly lower than that in the sn group ( 26.3% vs. 48.6% ; p<0.05 ) . 
 no significant differences were found between the two groups with regard to fertilization and pregnancy rates.conclusion:the newly designed needle significantly reduced pain and vaginal bleeding associated with single - follicle opu in patients receiving no analgesic treatment , in comparison with a standard needle . 
 the rn had no adverse effect on the quality of retrieved oocytes . 
Introduction
Methods
None
Patients:
Oocyte aspiration:
Rating of pain and evaluation of bleeding
Primary endpoint:
Secondary endpoint:
IVF procedure and embryo transfer:
Sample size calculation and statistical analysis:
Results
Discussion
Conclusion