Human Reproduction vol 11 no 9 pp 1881-1883, 1996 Transfer of gametes into the Fallopian tubes — is choice of side important? Geoffrey L.Driscoll1, John P.P.Tyler, Leon Clark and Joel Bernstein City West IVF, 12 Caroline St, Westmead, NSW 2145, Australia 'To whom correspondence should be addressed The aim of this study was to define pregnancy rates for gamete intra-Fallopian transfer (GIFT) with respect to the ovary from which most oocytes were collected (i.e. a gross index of ovarian stimulation) and the Fallopian tube (ipsilateral or contralateral) into which gametes were replaced. The only inclusion criterion was the ability to transfer gametes into the Fallopian tubes at GIFT. No other factors that could influence outcome were considered. In this retrospective review of the clinic's database, no relationship was found between pregnancy rate and placement of gametes into the Fallopian tube coincident with the ovary from which most oocytes were collected. Thus when performing unilateral tubal transfer at GIFT gametes may be returned to the side most convenient to the operating surgeon without fear of compromising pregnancy potential. Key words: Fallopian tube/gamete intra-Fallopian transfer/ GIFT Introduction With improvement in success rates of assisted reproductive techniques combined with the ability to cryopreserve surplus embryos, many clinics have reduced the number of embryos transferred in the cycle in which follicular stimulation has been induced. Thus in Australia the number of embryos transferred has reduced from four or more in 1986 (Fertility Society of Australia, 1987) to three and usually less as a recommendation of the Australian accrediting authority (Reproductive Technology Accreditation Committee, 1992). Similarly, in gamete intra-Fallopian transfer (GIFT), the practice of transferring gametes to both Fallopian tubes, as originally described (Asch et al., 1984; Leeton et al., 1987), has generally been abandoned in Australia and oocytes and spermatozoa are returned to the most accessible tube as long as there is no perceived or known dysfunction on that side. Most recent publications on GIFT make no note of unilateral or bilateral transfer and those few studies that have specifically examined unilateral transfer have relatively small data sets (Haines and O'Shea, 1989, 1991). The aim of this retrospective study was to test the hypothesis that potential for pregnancy was maximal if gametes were replaced into the Fallopian tube on the side coincident with © European Society for Human Reproduction and Embryology maximal ovarian stimulation, as defined by the collection of most oocytes from that side. Materials and methods All treatment cycles on the City West IVFs database (including patients who had multiple attempts) were reviewed for this study but treatments in which oocytes were received from a donor, transferred to both Fallopian tubes, or were collected from the Pouch of Douglas were omitted. Similarly, women who did not elect to use ovulation induction drugs were also excluded and because there were so few cases (n = 12) were not used as a comparison group Apart from these exclusions, no account was taken of other factors known to contribute to the overall pregnancy rate, such as the woman's age (range 22.1—48 7 years, median 32 3 years), body mass index (range 9.3-84.7, median 21.7), the type of ovanan stimulation used [clomiphene citrate (Clomid), Manon Merrell Dow, Frenchs Forest, NSW, Australia; leuprorelin acetate (Lucrin), Abbott Australasia, Kumell, NSW, Australia, or nafarelin acetate (Syneral), Searle, Crows Nest, NSW, Australia, m combination with either human menopausal gonadotrophin (HMG) or follicle stimulating hormone (FSH)' number of 75 IU ampoules used ranged between 5-136 with a median of 20] or the subsequent response of the ovary as determined by maximal oestrogen concentration in circulating peripheral plasma (range 809-21 100 pmol/1, median 6120) or the number of oocytes collected (left ovary: range 0-28, median 3; right ovary: range 0-18, median 3). Similarly, different operative methods for retrieving the oocytes (ultrasound guidance or laparoscopy), the type of catheter used for gamete transfer and the potentially differing techniques of the performing surgeon and embryologist were not taken into consideration, given that these data were collected over a 6 year period The male partner's potential fertility was also ignored as long as spermatozoa were deemed suitable Thus the inclusion criterion for data in this study was simply the ability to transfer gametes of 'visible' (but unknown) quality into the Fallopian tubes at GIFT The final database for review contained 1582 completed GIFT attempts. These data were sorted according to the difference in oocyte numbers collected from each ovary (with no account being taken of the total number of oocytes collected) and then classified as either left or right dominant Transfer at GIFT was considered ipsilateral if performed on the dominant side or contralateral if not For the majority of treatments (n = 1007; 63.7%), three oocytes were transferred, thus minimizing any major effect of oocyte number on pregnancy rate [29 (1.8%) had four oocytes returned, 432 (27.3%) had two oocytes returned and 114 (7.2%) had only one oocyte replaced]. Finally, in order not to skew results, data from women who only had oocytes collected from one side were segregated as it was not possible to differenuate on the database between poor stimulation or the absence of an ovary on one side Results After data selection 199 women had oocytes collected from only one ovary and 1383 had complete information that was 1881 GXJJriscoU et al L minus R 20 0- Lett Ovary Dominant Right Ovary Dominant -14 i 000% 50 362% 100 150 Frequancy 723% 1085% % of Total 200 250 1446% 1808% Figure 1. The distribution of the difference between the number of oocytes collected from the right (R) and left (L) ovaries (negative values mean more oocytes were collected from the right than from the left). available for review. The distribution of the difference in the total number of oocytes collected from each ovary (number collected from the left side minus number collected from the right side) in the latter group is shown in Figure 1. Negative values therefore correspond to more oocytes being collected from the right ovary than the left. Thus the data have a slight skew to right ovary predominance [with the interquartile range being 3 (-2-1) oocytes difference, the 10th and 90th percentile being - 4 and 3 respectively]. Only 20.8% of cases had a difference greater than three oocytes. The range of oocytes collected from both ovaries was 1-36 with a median collection of 7.0 cells. Table I summarizes the data and lists the pregnancy rates according to difference in oocyte number when gametes are replaced in either the ipsilateral or contralateral Fallopian tube. Numbers in each group are expressed as the number of pregnancies per total number of events exhibiting that response. When the data were combined such that pregnancy rate could be compared with transfer to either the ipsilateral or contralateral tube to the ovary yielding most oocytes, then 180/633 became pregnant with ipsilateral transfer (28.4%) and 153/547 became pregnant after contralateral transfer (27.9%). Chi-squared analysis showed this difference to be non-significant. Similarly, if only the extremes of oocyte difference were considered (i.e. more than three oocytes difference), again no significant difference was demonstrated (contralateral 467164:28.0%; ipsilateral 37/123:30.1%). At the other extreme, when no oocytes were collected from one ovary, overall pregnancy rates were reduced (17.1%) but no significant difference was found regarding the side of gamete transfer (15/103 versus 19/96). Discussion With the near universal use of ultrasound-guided transvaginal oocyte collection, the proportion of assisted reproductive 1882 technique cycles where supplementary laparoscopy for GIFT is performed appears to be reducing but still accounts for 35.8% of all assisted reproductive technique treatments in Australia (Fertility Society of Australia, 1995). This, coupled with the option of transvaginal GIFT (Jansen and Anderson, 1993) and its continuing refinement (Woolcott and Stanger, 1994; Woolcott et al, 1994), continues to make relevant the question posed in this paper. This retrospective review of assisted reproductive technique data was not conducted in an attempt to study Fallopian tube function but to provide reassurance of something hoped to be true by practitioners of GIFT. However, pregnancy outcome when gametes (or embryos) are placed in contralateral Fallopian tubes to the maximally stimulated ovary has not to the authors' knowledge been fully examined and, in the few studies on unilateral tubal transfer, no account has been taken of the side of transfer relative to ovarian stimulation (Haines and O'Shea, 1991). While it is known that ectopic pregnancies can occur on the contralateral tube to the ovulating ovary, and that in women with premature ovarian failure the Fallopian tube can transport gametes and pregnancies can occur when donated oocytes are used (Olar et al, 1989), subtle interactions between the ovulating ovary, its oocytes and Fallopian tube may exist An indication for this has recently been suggested by Kunz et al. (1996), when they demonstrated by hysterosalpingoscintigraphy preferential transport of spermatozoa into the tube ipsilateral to the dominant follicle, confirming the findings of Williams et al. (1993) that the number of spermatozoa associated with ovulation was also highest in the ipsilateral tube. This study also only examined a gross index of ovarian stimulation (i.e. difference in oocyte numbers collected from each ovary) and did not take into account many factors that are known to influence pregnancy rate such as female age and body mass index etc. Similarly, it is accepted that the ovary from which the majority of oocytes were collected was not necessarily the most 'stimulated' ovary from a biological viewpoint and, unlike Kunz et al (1996) and Williams et al. (1993) who related their data to a single dominant follicle, these data have been collected from patients in whom both ovaries underwent stimulation. However, even when the difference in the number of oocytes collected from each ovary was large (including the extreme when no oocytes were collected from one side) the hypothesis that transfer to the ipsilateral Fallopian tube would provide the maximal pregnancy rate did not hold. Similarly, given that variables known to affect pregnancy potential (i.e. female age) were relatively evenly distributed across the difference in oocyte groupings, then it was unlikely that any other subdivision of the data would change the finding. A factor which could not be ignored in this data review was the tendency of the operating surgeon to replace gametes into the right Fallopian tube (1100 transfers to right, 283 to left side, i.e. a ratio of 3.9:1). This was possibly because of each surgeon's right-handedness and easier access because of the descending sigmoid colon on the left side. Where oocytes were transferred to the left Fallopian tube there were specific reasons including easier access, better visual quality of the Ovarian response and unilateral GIFT Table I. Summary data for pregnancy rate according to the ovary (L = left, R = right) from which oocytes were collected and Fallopian tubes to which they were replaced Thus L = 3 > R means three more oocytes collected from the left than from the right ovary Ovanan 'response' R L R R R R R R R L L L L L L = = = = = = = * > = = = = = > 0 0 L 1> L 2 > L 3> L 4 > L 5 > L* L Total 1> R 2 > R 3 > R 4 > R 5 > R* R Total Transfer to left side Pregnancy ratio R L Transfer to right side Pregnancies/ total number % Pregnancy rate Pregnancies/ total number %Pregnancy rate 4/24 3/16 15/45 9/39 11/28 3/23 5/13 5/17 33/120 10/40 6723 16 7 188 33 3 23.1 39 3 13 0 38 5 29 4 27 5 250 26 1 35 0 22 2 30 8 27 9 16/80 11/79 39/158 41/172 37/130 33/84 10/55 26/74 147/515 41/161 32/112 20/61 7/31 20/62 120/427 20 0 139 24.7 23 8 28 5 39 2 18 2 35 1 28 5 255 28.6 32 8 22 6 32.3 28 1 7/20 2/9 8/26 33/118 1 030 0 725 0 742 1030 0 725 3 015 0473 1 194 1036 1020 1096 0.937 1018 1049 1007 •The small number of cases where oocyte number differences were > 5 (see Figure 1) have been combined with this grouping fimbria, previous ectopic pregnancy or known pathology or blockage on the other side. Similarly, each surgeon also had a preferred side from which he started puncturing follicles, but this does not appear to have disadvantaged a patient's potential for pregnancy. It is interesting to speculate whether returning oocytes collected from the 'dominant' ovary to the ipsilateral Fallopian tube may have improved pregnancy rates but since the source of the oocytes returned at GIFT was random (oocytes were ranked according to the size of the follicle from which they were aspirated and by visual features which embryologists consider optimal before selection of the 'best' for return), this was not possible. In conclusion, the results of this retrospective review of assisted reproductive technique data from a non-randomized approach to gamete replacement indicate that pregnancy rate is not influenced by the choice of Fallopian tube in which gametes are replaced at GIFT, and that the operating surgeon may utilize the most convenient tube without fear of compromising a patient's pregnancy potential. Acknowledgement The authors are grateful to Mr N. Crockett of the Statistics Dept, School of Economics, Macquane University, NSW, Australia, for statistical assistance in preparing this manuscript gamete intrafallopian transfer a case-controlled retrospective comparison FemL Stenl, 59, 836-840 Kunz, G , Beil, D , Deuunger, H et aL (1996) The dynamics of rapid sperm transport through the female genital tract evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Hum. Reprod, 11, 627-632 Leeton, J , Rogers, P, Caro, C et aL (1987) A controlled study between the use of gamete intrafallopian transfer (GIFT) and in vitro fertilisation and embryo transfer in the management of ldiopathic and male infertility. Feml Stenl, 48, 605-607 Olar, T T , Dickey, R P , Curole, D N and Taylor, S N (1989) Case report pregnancies established by gamete intrafallopian transfer and pronuclearstage transfer in patients with premature ovanan failure using donated oocytes and low-dose oral micronized oestradiol and progesterone /. In Vitro Fert. Embryo Transf., 6, 160-163. Reproductive Technology Accreditation Committee (1992) Guidelines for Assisted Reproductive Techniques Units in Australia. Fertility Society of Australia. Williams, M , Hill, C J , Scudamore, I et al (1993) Sperm numbers and distribution within the human Fallopian tube around ovuladon Hum. Reprod, 8, 2019-2026 Wbolcott, R. and Stanger, J (1994) The fluid dynamics of injection variables as they relate to transvaginal gamete intra-Fallopian transfer and tubal embryo transfer Hum. Reprod., 9, 1670-1672 Woolcott, R , Stanger, J , Cohen, R and Silber, S (1994) Refinements in the methodology of injection for transvaginal gamete mtra-Fallopian transfer Hum. Reprod, 9, 1466-1468 Received on January 25, 1996; accepted on June 7, 1996 References Asch, R., Ellsworth, L., Balmaceda, J and Wong, P (1984) Pregnancy after translaparoscopic gamete intrafallopian transfer Lancet, 2, 1034 Fertility Society of Australia (1987) fVF and GIFT pregnancies in Australia and New Zealand 1986 National Perinatal Statistics Unit, Sydney Fertility Society of Australia (1995) Assisted Conception Australia and New Zealand 1992 and 1993 National Perinatal Statistics Unit, Sydney Haines, CJ and O'Shea, R.T (1989) Unilateral gamete intrafallopian transfer the preferred method7 FertiL Stenl, 51, 518-519 Haines, CJ. and O'Shea, R.T (1991) The effect of unilateral versus bilateral tubal cannulation and the number of oocytes transferred on the outcome of gamete intrafallopian transfer. FertiL Stenl., 55, 423-425 Jansen, RP.S and Anderson, J C. (1993) Transvaginal versus laparoscopic 1883
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