A prospective randomized study comparing needles of different diameters for transvaginal ultrasound-directed follicle aspiration

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1 FERTILITY AND STERILITY Copyright 1996 American Society for Reproductive Medicine Printed on acid-free paper in U. S. A. A prospective randomized study comparing needles of different diameters for transvaginal ultrasound-directed follicle aspiration Awoniyi Awonuga, M.B., B.S.* John Waterstone, M.B., B.Ch. Olufunso Oyesanya, M.B., B.S. Ruth Curson, M.B., B.Chir. Geeta Nargund, M.B., B.S. John Parsons, M.B., Ch.B. Assisted Conception Unit, Department of Obstetrics and Gynecology, King's College School of Medicine and Dentistry, London, United Kingdom Objective: To determine whether the use of smaller diameter needles at oocyte collection reduces pain without jeopardizing the treatment outcome. Design: Prospective randomized study. Setting: The Assisted Conception Unit, Kings College Hospital, United Kingdom. Patients: One hundred twelve patients undergoing an IVF-ET treatment cycle. Interventions: Study patients were aged ::s38 years and had at least six follicles> 14 mm on the day of oocyte collection. Patients were randomized to follicle aspiration with a 15- (n = 34), 17- (n = 41), or 18- (n = 37) gauge (g) single channel needle. Intravenous pethidine and diazepam were used for analgesia and sedation. Pain was quantified by means of questionnaires completed by the patient and by her partner postoperatively. Results: A greater proportion of patients reported severe to unbearable pain with the 15- gauge compared with the 17-gauge (44% versus 22%) or 18-gauge (44% versus 16%) needles. Partners' perception of severe pain experienced by patients showed the same trend when the 15-gauge was compared with the 17- (62% versus 29%) and 18-gauge (62% versus 22%) needles. There was no significant difference between the needles regarding the oocyte collection rate, fertilization rate, proportion of oocytes with fractured zonae, cleavage rate, implantation rate, and pregnancy rate per cycle. Conclusions: Reducing the size of the needle used for oocyte collection from 15 to 17 or 18 gauge reduces pain without affecting the number of oocytes collected, their quality, or the clinical pregnancy rate. Fertil Steril 1996;65: Key Words: Needles, intravenous analgesia, oocytes collection, pregnancy The introduction of ultrasound (US)-guided follicle aspiration for oocyte collection using a vaginal transducer equipped with a needle guide (1) and IV analgesia (2) has radically simplified IVF-ET treatment. It is by far the most widely used method of oocyte collection for IVF-ET today (2). However, oocyte collection without general anaesthesia remains an uncomfortable procedure for many patients and the amount of pain involved must be minimized. Variables that determine the amount of pain experienced at oocyte recovery include the duration of the procedure, needle gauge, and the operator experience. We Received December 27, 1994; revised and accepted July 14, * Reprint requests: Awoniyi Awonuga, M.R.C.O.G., Midland Fertility Services, Centre House, Court Parade, Aldridge WS9 8LT United Kingdom (FAX: ). have established previously that the procedure can be shortened considerably without compromising oocyte collection rate by omitting follicle flushing (3). Although oocyte collection rates varying from 46% to 90% per follicle have been reported (4, 5), the relationship between needle size and oocyte collection rate is uncertain (6). A recent study (7) has suggested that 18-gauge (g) needles cause less pain than 16-g needles. Most needles in use today for IVF-ET are 15 g. This study sets out to determine if the use of a 17- or 18-g needle would reduce pain at transvaginal US-directed follicle aspiration without reducing the oocyte collection rate or increasing the number of damaged oocytes. MATERIALS AND METHODS One hundred twelve patients undergoing routine IVF treatment between January and July 1993 at Awonuga et a1. Needle size and oocyte collection 109

2 , the Assisted Conception Unit, King's College Hospital were studied after obtaining Ethical Committee approval. Patients were excluded from the study if they were >38 years of age, had only one ovary present, or had less than six follicles with mean follicular diameter> 14 mm on the day of transvaginal USdirected follicle aspiration. Patients were allocated randomly on the day of oocyte collection to follicle aspiration with a 15-, 17-, or 18-g single channel needle (Casmed, Cheam, Surrey, United Kingdom). All patients underwent similar ovarian superovulation therapy, which consisted of down-regulation with buserelin acetate (Suprefact; Hoechst, Hounslow, United Kingdom) for 2 weeks to which hmg (Pergonal; Serono, Welwyn-Garden-City, United Kingdom), two to six ampules per day, was added. Buserelin acetate and hmg were stopped, and 10,000 IU ofhcg (Profasi; Serono) were given when the mean diameter of the leading follicle was 2: 18 mm. Transvaginal US-directed follicle aspiration was performed 34 to 38 hours after hcg injection. Oral premedication with 1 mg lorazepam (Ativan; Wyeth Laboratories, Taplow, United Kingdom) was taken on the evening before transvaginal US-directed follicle aspiration and repeated 1 hour preoperatively. Pain relief and sedation during the procedure were achieved by the administration of 25 to 100 mg IV pethidine and 2.5 to 10 mg diazepam (Diazemuls; Dumex, Tring, Herts, United Kingdom) in incremental doses of 25 and 2.5 mg, respectively, as required. A mechanical sector scanner (Bruel and Kjaer, Naerum, Denmark) with a 7.0-MHz vaginal transducer and attached needle guide was used and aspirated follicles were not flushed. The outer and inner diameters of the 15-, 17-, and 18-g needles were 1.83 and 1.37, 1.47 and 1.07, and 1.27 and 0.84 mm, respectively. The sharp collecting tip ofthe needles was bevelled at an angle of 45 to the longitudinal axis of the needle. The other end of the 17 -and 18-g needles was attached to a length of Teflon tubing of a gauge corresponding to the needle gauge. With the 15-g needle, a short length of soft silicone rubber tubing was interposed between the needle and 17-g plastic tubing. A suction pressure of 100 mm Hg generated by a Craft suction pump (Rocket of London, Watford, United Kingdom) was used for the 15- and 17 -g needles and 150 mm Hg was used for the 18-g needle. All follicles with a mean follicular diameter > 10 mm were aspirated. The time taken for follicle aspiration, the number of follicles aspirated, and the number of oocytes collected was recorded, as well as the incidence of fractured zonae. Before departure from the unit (approximately 1 hour after the procedure), the patients and their partners were presented separately with a verbal analogue scale that graded pain as none, mild, moderate, severe, very severe, and unbearable. The patients also were asked if they felt pain occasionally, half, most, or all the time and whether they would prefer to have general anaesthesia next time. The partner's perception of patient's duration of pain and their preference for the patient to have general anaesthesia next time were noted. Semen preparation, insemination of oocytes, and embryo culture were performed using standard procedures. Fertilization status (number of pronuclei) was established by light microscopy 16 to 18 hours after insemination. A maximum of three embryos were transferred 2 days after oocyte collection. Each embryo transferred was given a score derived by multiplying the number of cells in the embryo by the grade of the embryo. The sum of the embryo scores of all the embryos transferred were added to give the cumulative embryo score (8). Patient's age was the only outcome measure that was distributed normally. Comparative analysis was performed with one-way analysis of variance for patient's age and Kruskal-Wallis test for other continuous data. X 2 test (with Yates' correction) was used for categorical data. All data available for each calculation were used. Missing data resulted in reduced numbers of values for some results. AP value < 0.05 was considered as significant. RESULTS There was no significant difference between the three groups of patients regarding age, gravidity, parity, duration of subfertility, or infertility diagnosis. The three groups were also comparable regarding the median number of ampules ofhmg used for superovulation. Six hundred fifteen, 650, and 571 follicles were aspirated using the 15-, 17-, and 18-g needles, respectively. There was no significant difference in the oocyte collection rate (percent of all follicles aspirated that yielded an egg) (66.2% versus 69.1% versus 62.2%), normal fertilization rate (percent of all oocytes inseminated that fertilized with two pronuclei) (52.1% versus 64.2% versus 56.8%), cleavage rate (percent of all oocytes with two pronuclei that cleaved normally) (85% versus 93.0% versus 90.8%), proportion of all oocytes with a fractured zona (6.1% versus 5.7% versus 5.4%), and those with polypronuclear fertilization (1.8% versus 2.9% versus 1.7%) and the implantation rate (percent of all embryos transferred that resulted in a clinical pregnancy) (14.8% versus 17.0% versus 13.3%) in the 15-, 17-, and 18-g needles, respectively. Also not significantly different were the median number of embryos avail- 110 Awonuga et al. Needle size and oocyte collection Fertility and Sterility

3 Table 1 Details of Treatment Cycles 15 g 17 g No. of patients No. of embryos available for transfer* 4 (0 to 14) 5 (1 to 21) No. of embryos transferred* 2 (0 to 3) 2 (0 to 3) Cumulative score of embryos transferred* 33 (12 to 64) 28 (8 to 96) Clinical pregnanciest 8 (24) 11 (27) * Values are medians with ranges in parentheses. t Values in parentheses are percentages per cycle g 4 (0 to 13) 2 (0 to 3) 32 (5 to 64) 11 (30) able or transferred, the cumulative embryo score, and the clinical pregnancy rate per cycle (Table 1). The median dose of pethidine (50 mg, range 25 to 100 mg; 50 mg, range 25 to 100 mg; 50 mg, range 25 to 100 mg) and diazepam (5 mg, range 2.5 to 12.5 mg; 5 mg, range 2.5 to 10 mg; 5 mg, range 2.5 to 10 mg) and the time taken for oocyte collection (9.15 minutes, range 2.5 to 22.B minutes; 9.2 minutes, range 2.5 to 16 minutes; 9.6 minutes, range 3.6 to 46.B minutes) were not significantly different in the 15-, 17- and 1B-g needle groups, respectively. However, a significantly greater proportion of patients in the 15-g compared with the 17-g (20.6% versus 4.9%; odds ratio [OR] = 0.2; 95% confidence interval [CI] = 0.01 to 0.31; P < 0.05) and compared with the 1B- g (20.6% versus 2.7%; OR = 0.1; CI = 0.03 to 0.32; P < 0.02) required the maximum dose of pethidine (100 mg) allowed for transvaginal US-directed follicle aspiration in our unit (Table 2). There was no difference in the proportion of patients requiring the maximum dose of pethidine between the 17- and 1B-g (4.9% versus 2.7%) needle groups. A significantly greater proportion of patients (44%) found that the use of the 15-g needle was associated with severe to unbearable pain compared with 22% in the 17-g (OR = 0.4; CI = 0.01 to 0.43; P < 0.05) and 16% in the 1B-g needle group (OR = 0.25; CI = O.OB to O.4B; P < 0.02). Similarly, a significantly higher proportion of partners of patients in the 15-g compared with 17-g (62% versus 29%; OR = 0.3; CI = 0.11 to 0.55; P < 0.01) and 1Bg needle (62% versus 22%; OR = 0.2; CI = 0.19 to 0.61; P < 0.001) reported that their spouses experienced severe to unbearable pain. There was no difference in pain perception by patients and partners when 17- and 1B-g needles were compared. A significantly higher proportion of partners in the 15-g needle group compared with those in the 17 -g (29% versus 11%; OR = 0.3; CI = to 0.37; P < 0.05) and 0% for the 1B-g group stated that their spouses were in pain most or all the time and a significantly higher proportion in the 15- compared with 18-g (41% versus 8%; OR = 8.7; CI = 0.14 to 0.52; P < 0.001) and 17- compared with 18-g needle (32% versus B%; OR = 5.1; CI = 0.04 to 0.44; P < 0.02) would prefer their spouse to have general anesthesia should they need to have the procedure again. Similar trends regarding the duration of pain and preference for general anesthesia in future were apparent for the patients but did not reach significance. There was no significant difference in the proportion of partners requesting general anesthesia next time when the 15-g was compared with 17 -g needle. Combining the data for all three needles and considering patients whose partners reported severe to unbearable pain, 60% of the patients agreed with their partner whereas 40% reported pain that was at most moderate. DISCUSSION A major disadvantage of transvaginal US-directed follicle aspiration without general anesthesia is the Table 2 Perception of Pain at US-Directed Follicle Aspiration 15 g 17 g 18 g Pain perception by patient: severe to unbearable pain Pain perception by partner: severe to unbearable pain Patient's perception of duration of pain: most to all of the time Partner's perception of duration of pain: most to all of the time Pain relief next time: Patient prefers general anesthesia Partner prefers general anesthesia * Values in parentheses are percentages. tp < :l:p < /34 (44)*t:l: 9/41 (22)t 6/37 (16):1: 21/34 (62) 11 11/38 (29) 8/36 (22)11 10/34 (29) 7/39 (18) 6/37 (16) 10/34 (29)t 4/38 (10.5)t 0/36 (0) 10/34 (29) 5/41 (12) 4/37 (11) 14/34 (41)11 12/38 (32):1: 3/36 (8):1:11 P < lip < AwoDuga et ai. Needle size and oocyte collection 111

4 variable degree of pain experienced by patients (3). Although operator skill, omission of follicle flushing and the administration of analgesia can minimize such discomfort, the size of the needle used remains a major factor. Provided oocytes are not damaged and the number recovered is not reduced, it would be advantageous to the patient ifthe size of the needles used for follicle aspiration could be reduced. Although the oocyte collection rate depends on the experience of the operator, other variables such as the internal diameter (ID) of the needle and the suction pressure applied also may be important. Evaluation of the effect of needle diameter and the vacuum pressure on the oocyte collection rate from previous studies gave contradictory conclusions. Lenz (6) reported that increasing the ID from 0.7 to 1.0 mm improved their oocyte collection rate. In that study, a syringe was used to apply vacuum pressure and, in an earlier study from the same institution (9), they observed fractured zonae in 5.1% ofthe oocytes using the syringe. Vacuum pressures of between 90 and 120 mm Hg have been recommended for oocyte collection (l0, 11). Lopata and colleagues (12), using a 20-g needle (probably 0.6 mm ID), found a higher collection rate by a vacuum pressure of 200 mm Hg (45.6%) compared with a vacuum pressure of 120 to 180 mm Hg (20.4%). A lower pressure reduced the collection rate, whereas a further increase (>200 mm Hg) resulted in morphologically abnormal 00- cytes. A previous randomized study in this unit (unpublished data) showed that, using a 15-g double channel needle (ID of aspirating channel 0.97 mm), there was no significant difference in either oocyte collection rate or incidence of fractured zonae when an aspiration pressure of 100 mm Hg was compared with one of 150 mm Hg. Preliminary experiments before the present study revealed that an aspiration pressure of 150 mm Hg was necessary for the 18-g needle in order to aspirate fluid at a similar rate as the 15- or 17 -g needles at a suction pressure of 100 mmhg. We found that the use of a 17- or 18- rather than a 15-g needle did not reduce the proportions of collected, viable, or fertilized oocytes; embryos transferred; or the clinical pregnancy rate per cycle. There was a significant reduction in the pain experienced by the patients and observed by their partners when the 17- or 18-g needle was used. Partners reported a greater degree of pain and a greater desire for future general anesthesia than did patients. A possible explanation for this discrepancy is that some degree of amnesia may follow IV administration of diazepam and patients might not have remembered fully the severity of the pain they felt. However, we believe that patients' preferences should take prior- ity over that of their partners as they were the one perceiving the pain. There was no significant difference in the time taken for the procedure and the amount of pethidine and diazepam used with the three needle sizes. However, a significantly greater proportion of patients in the 15-g needle group required the maximum dose of pethidine allowed for transvaginal US-directed follicle aspiration in our unit, which is further evidence that this needle size causes more pain. The patient's comfort is an important issue in transvaginal US-directed follicle aspiration. Because patients may need repeated attempts before pregnancy and live birth is achieved (5), it is important that patients and their partners are not left with unpleasant memories about the procedure. We have shown that reducing the size ofthe needle used to 18-g reduces pain experienced by the patient and perceived by their partners without causing any untoward effect on the oocytes recovered and does not affect the clinical pregnancy rate. Before the first attempt it is not possible to predict which patient will experience undue discomfort. In view of the risks and cost, our policy is not to offer general anesthesia for the first transvaginal US-directed follicle aspiration for egg collection but subsequently to offer general anesthesia to those patients who need one. Acknowledgments. The authors thank the medical, nursing, and scientific staff of the clinic for their help in this study. REFERENCES 1. Wikland M, Enk L, Hammarberg K. Transvesical and transvaginal approaches for the aspiration of follicles by use of ultrasound. Ann NY Acad Sci 1985;442: Tan S-L, Bennett S, Parsons J. Surgical techniques of oocyte collection and embryo transfer. 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