Embryo transfer by midwife or gynecologist: a prospective randomized study
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Acta Obstet Gynecol Scand 2003; 82: 462--466 Copyright # Acta Obstet Gynecol Scand 2003 Printed in Denmark. All rights reserved Acta Obstetricia et Gynecologica Scandinavica ISSN 0001-6349 ORIGINAL ARTICLE Embryo transfer by midwife or gynecologist: a prospective randomized study KERSTIN BJURESTEN, JULIUS G. HREINSSON, MARGARETA FRIDSTRÖM, BJÖRN ROSENLUND, INGVAR EK AND OUTI HOVATTA From the Department of Obstetrics and Gynaecology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden Acta Obstet Gynecol Scand 2003; 82: 462–466. # Acta Obstet Gynecol Scand 2003 Background. Embryo transfer (ET) in assisted reproduction treatments has traditionally been performed by gynecologists in the Nordic countries. As gynecologists often have a busy schedule, midwives and nurses have become increasingly important in performing the treatment, providing subject information, ultrasound monitoring and assistance at ET. As part of the continuous development of our IVF treatment we have carried out a prospective randomized pilot study where either a midwife or a gynecologist has performed ET. The aim of this study was to see if a skilled IVF midwife could perform ET with similar results to a gynecologist. Methods. On the day of oocyte aspiration the subjects were randomized, by means of closed envelopes, for ET to be performed either by a midwife or a gynecologist. A total of 102 subjects were included in the study, 51 for ET by a skilled midwife and 51 by a gynecologist. There were no differences in the groups in respect to ET routine and catheters used. Results. No significant differences were observed in subject characteristics as regards age, method of pituitary down-regulation or proportion of IVF/ICSI cycles. Similar clinical pregnancy rates between ETs performed by midwives vs. gynecologists, 31% vs. 29%, respectively, were seen. Subject experience as judged by a questionnaire also showed high acceptance of ET by a midwife. Conclusion. The results show that it is a feasible option to allow midwives to carry out ETs. Key words: midwife; embryo transfer; invited fertilisation; pregnancy Submitted 20 June, 2002 Accepted 11 November, 2002 Nurses and midwives take an active part in offering assisted reproductive techniques (ART), planning and organizing fertility treatments, gynecologists have traditionally performed informing the couples as well as performing vari- embryo transfers (ETs). They often have busy ous aspects of the clinical treatment such as schedules and midwives are available as active ultrasound scanning (1–3). In Swedish clinics participants during treatment. A Swedish mid- wife has education and experience in counselling. Abbreviations: They are also educated in the placement of ART: assisted reproductive techniques; ET: embryo transfer; intrauterine devices for prevention of pregnancy. FSH: follicle-stimulating hormone; GnRH: gonadotrophin- In many cases midwives perform intrauterine releasing hormone; hCG: human chorionic gonadotrophin; ICSI: intracytoplasmic sperm injection; IUI: intra-uterine insemination (4). This procedure is similar to insemination; IVF: in vitro fertilization; IVM: in vitro introducing an ET catheter into the uterine maturation; OPU: ovum pick up. cavity. In our Fertility Unit some of the midwives # Acta Obstet Gynecol Scand 82 (2003)
Embryo transfer by midwife or gynecologist 463 have experience in performing vaginal ultrasound Embryo quality and selection for ET was evalu- scanning for monitoring follicular development ated by using an original scoring system (7, 8). and for intrauterine insemination as well as Briefly, a maximum score of 3.5 was given to experience in assistance with abdominal ultrasono- embryos when no factors reducing embryo qual- graphy during the ET. Experience from the ity were observed. For each of the following UK shows that midwives can perform ETs factors, 0.5 was subtracted from the embryo without compromising pregnancy results (5, 6). score: > 10% fragmentation, > or < 4 cells on day As part of a developmental project in the Fertility 2, or > or < 8 cells on day 3, uneven size of blas- Unit we performed a prospective randomized tomeres, nonspherical blastomeres, cytoplasmic study to see if ET performed by midwives works anomalies, uneven cell membranes and a large in our circumstances. This was a pilot study to perivitelline space. Embryos with multinucleated show that a system where the midwives carry out blastomeres were avoided whenever possible. ETs works in the IVF unit of a large teaching hospital. Our clinical results and the experiences ET procedure of the subjects shows that it is feasible and highly acceptable to allow midwives to carry out ETs. All subjects for ET presented with a full urinary bladder to reduce the angle between the cervix and Materials and methods the uterus and to allow visualization in ultrasono- graphic scanning. Abdominal or vaginal ultrasono- Stimulation graphy was performed to check the position of the Pituitary-gonadal suppression was achieved with uterus, the size of the ovaries and for possible fluid in a GnRH agonist (buserelin, Suprecur1, Hoechst, the pouch of Douglas. A self-holding speculum was Frankfurt-am-Main, Germany) or an antagonist applied and the cervix was wiped with Hepes- (Cetrotide1, Asta Medica). Controlled ovarian buffered medium containing human serum albumin hyper-stimulation was induced using recombinant (Gamete, Vitrolife Gothenburg, Sweden). A mock follicle-stimulating hormone (FSH; Gonal F1, transfer was in most cases performed with a soft Serono Nordic, Stockholm, Sweden, or Puregon1, test-catheter (K-soft 5002 Cook, Queensland, Organon, Oss, the Netherlands). Ovulation was Australia). Catheters used for ET were Wallace induced by human chorionic gonadotrophin 1816 N (Sims Portex Ltd, Kent, UK) (midwife n ¼ (hCG; Profasi1, Serono or Pregnyl1,Organon) 25, gynecologist n ¼ 20) and Emtrac 4219 Delphin when the largest follicles had reached a diameter (Gynétics Medical Products N.V., Hamont-Achel, of at least 18 mm. The oocytes were retrieved by Belgium) (midwife n ¼ 19, gynecologist n ¼ 15). In transvaginal ultrasound-guided follicle aspiration cases of difficult passage through the cervical canal 37 h later. a K-jet 3205 (Cook, Queensland, Australia) (mid- In the midwife ICSI group there was one wife n ¼ 7, gynecologist n ¼ 14) was used. Twice in instance of IVM, involving short-term stimula- the gynecologist group a TDT catheter (Frydman, tion with low-dose Gonal-F1(Serono) without Neuilly, France) was used. With ultrasound agonist or antagonist treatment, to recover guidance (9, 10), one or two embryos were placed immature oocytes. The decision to perform insem- in the middle of the uterine cavity. Afterwards, the ination by standard IVF or by ICSI was based on catheter was flushed and checked for remaining sperm quality. On the day of oocyte aspiration embryos. In cases of unsuccessful transfer by the subjects were randomized, by using sealed midwife a gynecologist, present in the unit at all envelopes, to ET by either a midwife or a gyne- times, was called. cologist. Before ET, the couples were informed as The women were instructed to carry out a regards their embryo quality and possibility of pregnancy test (urine test kit) 20 days after OPU. embryo cryopreservation, as well as whether the For luteal phase support, vaginal progesterone ET was to be performed by a midwife or a (400 micrograms) was applied three times a day gynecologist. from day two after OPU until the pregnancy test. All pregnancies were later confirmed by vaginal ultrasonography and only clinical preg- Embryo culture nancies with gestational sacs were counted, i.e. a visible intrauterine sac with amniotic fluid, a yolk Oocytes and embryos were cultured in IVF- sac and a fetus with a heart beat. medium (Vitrolife1,Gothenburg,Sweden). Insem- The chi-square test and Fisher’s exact test were ination was performed in the afternoon of the day used in statistical comparison of the groups. A of oocyte aspiration. In most cases ET was per- p-value of < 0.05 was considered statistically formed on day two after ovum pick up (OPU). significant. # Acta Obstet Gynecol Scand 82 (2003)
464 K. Bjuresten et al. Questionnaire inations in the Obstetric Unit of the University Hospital. These midwives are also allowed to After ET, the subjects were asked to anonym- carry out vaginal ultrasonographic examinations, ously fill in a questionnaire regarding their which is an advantage in the current circumstances. experiences of the treatment. The questionnaire Monitoring of the ovaries before OPU, and early contained five questions. The first asked if it was pregnancy scanning approximately 6 weeks after their first ET or not. The next question concerned ET, is performed by midwives. Education and their experience with the midwife/gynecologist experience of ultrasound examinations are very during the ET. The third question was about the important in this context; for instance, before ET, information concerning embryos for ET and the position of the uterus, the size of the ovaries, embryos for possible cryopreservation. The two possible fluid in the pouch of Douglas, and where last questions regarded what to do until the preg- the catheter tip is situated during embryo transfer nancy test and how to carry it out. must be checked (9,10). The midwives who perform The questionnaire was based on a scale from 1 intra-uterine insemination (IUI) also have to exam- to 4: 1 ¼ poor; 2 ¼ acceptable; 3 ¼ good; 4 ¼ ine the ovaries before insemination, checking that excellent. there are no more than two developing follicles and checking for an anti- or retroflexed uterus. Intra- Results uterine insemination is a good training procedure for ET. A Swedish midwife is familiar with inserting One hundred and two subjects participated in the a self-retaining vaginal speculum visualizing the study, and after randomization there were 51 in cervix before introducing an intrauterine device each group. No significant differences were for prevention of pregnancy. The procedure is simi- observed regarding age, IVF/ICSI, average num- lar when performing ET. Continuous experience in ber of all oocytes and average number of all abdominal and vaginal ultrasonography is import- oocytes fertilized. The average embryo score was ant as regards successful ETs. similar in both groups, as was the average num- Introducing the couple to the IVF Unit, with ber of embryos for ET. There were no differences information on the IVF procedure, the injection in agonist vs. antagonist cycles between the two technique, assistance during OPU and ET, and groups. No significant differences were observed counseling, both by telephone and directly, has in clinical pregnancy rates between the midwife always by tradition been the work of a midwife. and gynecologist groups, 31% vs. 29%, respect- In the majority of units oocyte recovery and ively (Table I). embryo transfer have been performed by a gyne- A gynecologist was called twice, when the cologist. In the UK two studies have been pub- embryo transfer attempt by a midwife was unsuc- lished regarding nurses/midwives performing ET cessful. In one case there was difficulty in passing (5, 6). In Oxford, 771 ETs were reported. Nurses the cervix, and in the other case the subject had a had performed 679/771 (88%) and doctors 68/771 double uterus, with two cervical canals, of which (9%). one was blind. The clinical pregnancy rate after transfer by a The questionnaires were answered by 44 sub- nurse was 36.2% and the pregnancy rate after jects in the midwife group, and by 30 subjects in transfer by a doctor was 29.4%. In Birmingham the gynecologist group. Most subjects responded during 1996/1997, a clinical pregnancy rate/ET of to the questions with scores of 3 ¼ good and 4 ¼ 29.4% was reported when performed by nurses, excellent. Of those who responded, 19 in the mid- and it was 31.8% when performed by doctors. wife group and 18 in the gynecologist group were These pregnancy rates in the two studies were undergoing their first ET, while 25 in the midwife similar. Our study confirmed those results, with group and 12 in the gynecologist group had the clinical pregnancy rate/ET performed by a already undergone it. There were no differences midwife (31%) and by a gynecologist (29%) regarding experiences with the gynecologist or being similar. The total number of ETs was too midwife during ET information regarding low to show a statistical difference, but the equal embryos for ET or cryopreservation, or informa- numbers show good feasibility of ET by mid- tion regarding the pregnancy test (Table II). wives. Embryo transfer performed by midwives is a good development for the midwives themselves Discussion and for IVF Units in countries such as Sweden Some of the midwives in our IVF Unit have had and UK where the midwives have an education several years of education and experience of for carrying out procedures independently. Most abdominal and diagnostic ultrasonographic exam- important is proper training and education in # Acta Obstet Gynecol Scand 82 (2003)
Embryo transfer by midwife or gynecologist 465 Table I. Subject characteristics and outcome of treatment in the two groups Midwife group Gynecologist group n ¼ 51 n ¼ 51 Mean age SD 32.8 3.3 33.1 3.8 No. of IVF cycles 22 (43%) 30 (59%) No. of ICSI cycles 29 (57%) 21 (41%) Agonist cycles 35 (69%) 39 (76%) Antagonist cycles 15 (29%) 12 (24%) Average no. of all oocytes IVF 14.2 ICSI 13.9 IVF 14.8 ICSI 11.2 Average no. of all fertilized IVF 5.4 ICSI 7.6 IVF 9.5 ICSI 5.4 Average score of all embryos IVF 2.3 ICSI 2.2 IVF 2.2 ICSI 2.2 Day of ET Day 2 Day 3 Day 5 Day 2 Day 3 Day 5 No. of IVF performances 18 4 0 23 5 2 No. of ICSI performances 27 1 1 19 1 1 Average score of embryos for ET IVF 2.7 ICSI 2.4 IVF 2.6 ICSI 2.3 Average no. of embryos for ET IVF 1.6 ICSI 1.6 IVF 1.7 ICSI 1.7 ET ¼ embryo transfer; ICSI ¼ intracytoplasmic sperm injection; IVF ¼ in vitro fertilization. performing ET, with backup by a gynecologist it is feasible that midwives can carry out ETs, the always being available in the IVF clinic. number of ETs in our study can be regarded as The gynecologists have to continue to carry out sufficient. This study shows that ET by an experi- a part of the ETs in order to be able to perform enced midwife can be performed without com- difficult transfers. On the other hand, according promising clinical pregnancy rates. This is in to our experience, midwives also learn to carry agreement with reports from the UK (5, 6). Our out difficult ETs when gaining experience. Our study also shows that subjects are satisfied with a study was a prospective randomized study, midwife performing ETs (Table II). because we thought that randomization was the most objective method to share the patients between the gynecologists and the midwives. In Conclusion such an approach we did not need a power to show differences between pregnancy rates at the Our results show that specially trained and level of, for instance, 5%, for which 400 cycles in experienced midwives with knowledge of ART, each arm would have been needed. To show that ultrasonography, and oocyte and embryo Table II. Scores in the questionnaire Questionnaire answers Midwife group Gynecologist group n ¼ 44 of 51 (86%) n ¼ 30 of 51 (59%) Previous ET 25 subjects 12 subjects Experience with gynecologist/midwife during ET 1¼0 1¼0 2¼0 2¼0 3¼0 3 ¼ 3 (10%) 4 ¼ 44 (100%) 4 ¼ 27 (90%) Information on embryos for ET 1¼0 1¼0 2¼0 2 ¼ 2 (6%) 3 ¼ 4 (9%) 3 ¼ 11 (37%) 4 ¼ 40 (91%) 4 ¼ 17 (57%) Information on the period before the pregnancy test 1¼0 1¼0 2¼0 2 ¼ 3 (10%) 3 ¼ 6 (14%) 3 ¼ 7 (23%) 4 ¼ 38 (86%) 4 ¼ 20 (67%) Information on the pregnancy test 1¼0 1¼0 2 ¼ 1 (2%) 2¼0 3 ¼ 9 (21%) 3 ¼ 12 (40%) 4 ¼ 34 (77%) 4 ¼ 18 (60%) Scale 1–4: 1 ¼ poor; 2 ¼ acceptable; 3 ¼ good; 4 ¼ excellent. ET ¼ embryo transfer. # Acta Obstet Gynecol Scand 82 (2003)
466 K. Bjuresten et al. development can successfully perform embryo Birmingham experience. Hum Reprod 1998; 13: transfers without compromising pregnancy 699–702. 7. Mohr LR, Trounson A. Cryopreservation of human results. In the future we are going to extend the embryos. Ann N Y Acad Sciences 1985; 442: 536–43. program by letting midwives carry out all ETs. 8. Fridström M, Carlström K, Sjöblom P, Hillensjö T. Effects of prednisolone on serum and follicular fluid androgen levels in women with polycystic ovary syn- Acknowledgments drome undergoing in vitro fertilization. Hum Reprod 1999; 14: 1440–4. We thank the gynecologists, midwives and laboratory staff 9. Coroleu B, Carreras O, Veiga A, Martell A, Martinez F of the Fertility Unit for support during this study. et al. Embryo transfer under ultrasound guidance improves pregnancy rates after in-vitro fertilization. Hum Reprod 2000; 15: 616–20. References 10. Wood EG, Batzer FR, Go KJ, Gutmann JN, Corson SL. Ultrasound-guided soft catheter embryo transfers will 1. Ashcroft S. Developing the clinical nurse specialist’s role improve pregnancy rates in in-vitro fertilization. Hum in fertility: do benefit? Hum Fertil (Camb) 2000; 3: Reprod 2000; 15: 107–12. 265–7. 2. Birch H. The extended role of the nurse-opportunity or threat? Hum Fertil (Camb) 2001; 4: 138–44. 3. Barber D. Research into the role of fertility nurses for the development of guidelines for clinical practice. Hum Reprod 1997; 12: 195–7. Address for correspondence: 4. Morris EJ. The role of infertility nurses in an ovulation Kerstin Bjuresten induction program. Hum Fertil (Camb) 2001; 4: 14–7. Department of Obstetrics and Gynaecology 5. Barber D, Egan D, Ross C, Evans B, Barlow D. Nurses Karolinska Institute performing embryo transfer. successful outcome of Huddinge University Hospital fertilization. Hum Reprod 1996; 11: 105–8. Stockholm 6. Sinclair L, Morgan C, Lashen H. Nurses performing Sweden embryo transfer. The development and results of the e-mail: Kerstin.Bjuresten@hs.se # Acta Obstet Gynecol Scand 82 (2003)
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