JBRA Assist. Reprod. 1999;03(02):14-15
ARTIGO ORIGINAL

doi: 10.5935/1518-0557.1999.3.2.04

Tansferência direta de óvulos e espermatozóides, uma opção útil no tratamento de pacientes que falharam após hiperestimulação ovariana controlada

Direct ovum transfer, an useful treatment option for patients who have failed empirical controlled ovarian hyperstimulation

S. Lee1,2, I. A. Treharne1, W. Carvalho2

1TRACC, 55 Turner Road, Colchester, Essex
2Portland Hospital Fertility Unit, Portland Hospital Fertility Unit

Correspondence to:
S Lee PhD FIBMS, Portland Hospital Fertility Unit
Portland Hospital Fertility Unit
E-Mail: SammyLee@compuserve.com
Fax: 0171 383 0090 or
Address: W Carvalho MD, Universidade Federal Paulista
São Paulo
Brazil

Abstract
Introduction: Direct ovum transfer (DOT) has been reinvestigated (after modifications to the methodology) with a view to offering patients who had failed controlled ovarian hyperstimulation (COH) treatment further chances of active management prior to IVF referal.
Materials and Methods: In all, 19 couples were treated with 40 cycles of DOT. In order to provide some control data for comparison, results from the IUI programme (during the same time period) were also included. Controlled ovarian hyperstimulation and ovulation was monitored by ultrasound only. The sare COH regimen was used for both IUI and DOT. Similarly, the same method of semen preparation was used for both. Oocyte recovery was done transvaginally. Patients were sedated using Pethidine and Hypnovel. Two ova and approximatedly 20 000 sperms were then loaded, in 100-150 ul of medium, into a catheter and then placed directly into the uterus via the cervix.
Results: From 40 completed DOT cycles seven pregnancies have been established. Amongst IUI patients treated on the same day, six pregnancies were established out of 125 cycles (significant, p<0.04).
Conclusion: The additional modifications of the treatment procedure have further simplified the method. The encouraging results indicate that DOT may be an useful treatment option for COH failures. A larger study is needed.

Keywords: Ovum transfer, treatment

Introduction
The reproduction revolution of the 80s has produced great changes. In recent years, controlled ovarian hyperstimulation (COH) with and without intrauterine insemination have become popular empirical treatments (Davies et al., 1988; Mascarenhas et al., 1994), but most patients still fail to succeed. This clinical experience with direct ovum transfer (DOT); a reinvestigation of a method Craft et al., 1982 first described in the eighties (with modifications, such as transvaginal ultrasound, instead of laparoscopy and immediate transfer of gametes instead of six hour delay), has been carried out to determine its potential role as an outpatient clinic procedure for COH failures.

Materials and Methods
All patients underwent screening in accordance with the protocol outlined in the Royal College of Obstetricians and Gynaecologists publication, Infertility: Guidelines for practice (1993).
The mean age of the couples was 33.5 years (range 28-38), all had a duration of unexplained infertility of 3 years or more (all having previously failed six cycles of empirical controlled ovarian hyperstimulation, the last three with IUI). In all, 19 couples were treated with 40 cycles of DOT. In order to provide some control data for comparison, results from the IUI programme (treatments carried out over the sare time period as the DOT treatments) have also been included (70 couples with unexplained infertility; 125 treatment cycles; mean age 32, range 26-37) of at least 2.5 years standing.
Oocyte retrieval (OR) was restricted to one session per week, necessitating patient cycle manipulation with Buserelin (by nasal spray, about 1 mg per day, Suprefact, Hoechst, UK); used as they commenced menses. Once the ultimate patient had started menses, all other patients would be synchronised with this one. Metrodin (Serono, Welwyn Garden City, UK) would then be administered a fortnight ahead of the day of OR. Controlled ovarian hyperstimulation and ovulation, determined by ultrasound only (ALOKA 500, Southend, UK), was done a previously described treatments (Davies et al., 1988; Mascarenhas et al., 1994). Five cycles were lost to DOT, because of inadequate response (5 out of 45; 11. 1%). Our concerns about multiple pregnancy and its related complications has meant that the same COH regimen has been used for both IUI and DOT. Similarly, the same method of semen preparation was used for both IUI and DOT treatments (Davies et al., 1988).
Oocyte recovery (using disposable needles and tubing sets obtained from SIMS-Wallace, Colchester, UK; done transvaginally, using the Aloka ultrasound) was done in a theatre designed for day case procedures, took just 20-35 minutes. Patients were sedated using up to 100mg Pethidine (Roche, Welwyn Garden City, UK) and up to 20mg Hypnovel (Roche, Welwyn Garden City, UK). Two ova and approximatedly 20 000 sperms were then loaded, in 100-150 ul of medium, into an embryo replacement catheter (SIMS-Wallace, Colchester, UK). Ova and/or sperms were then placed directly into the uterus via the cervix.
Statistical analysis done using computer software (Instat, GraphPad, San Diego, USA) by chi-squared test (with Yate's correction).

Results
From 40 completed DOT cycles (19 couples) seven pregnancies (18%, 4 delivered, 2 miscarried, 1 ongoing; one set of twins safely delivered and the rest singletons) have been established. Amongst IUI patients treated on the sare day as the DOT patients (125 cycles; 70 couples) six pregnancies were established. (4.8%, statistically significant, as determined by analysis using Chi-squared 2x2 contingency tables, p<0.04).

Discussion
A delivery rate of about 13% per cycle is encouraging. Bearing in mind that all these couples had previously failed 6 cycles of COH (3 with IUI) treatments (see Davies et al., 1988; Mascarenhas et al., 1994), and that it was significantly better than results for patients on our IUI programme during the sare period, we feel sufficiently encouraged that DOT offers couples further hope of treatment after IUI failure.
In conclusion, the further simplifications used in this reinvestigation of DOT have produced results which indicate that it may be of value as a simple outpatient procedure for patients with unexplained infertility who have failed empirical COH. Clearly, an expanded study with more careful design and better controls is needed. Nevertheless, we are sufficiently encouraged to have adopted DOT as a routine procedure in our clinic.

Acknowledgements
Waldemar Carvalho would like to acknowledge the following: the support by way of a travelling bursary from the Botucatu Medical School (for WC), the kind help and advice from Professor JG Franco Jr, Sue Smith and Kathryn Parkinson of the Portland Hospital for allowing me access to the excellent facilities and lastly, but by no means least, all the staff at the Portland Hospital Fertility Unit for their kindness and hospitality.

References
Craft I., Djahanbakhch O., McLeod F., Bernard A., Green S., Twigg H.- Human pregnancy following oocyte and sperm transfer to the uterus. Lancet 1982: i, 1031-3.

Davies W. A. R., Dhariwal H. S., Lee S. - GIFT and IUI in the district general hospital. Human Reprod 1988; 3: 611-2.

Mascarenhas L. Khastgir G., Davies W. A. R., Lee S.. Controlled Ovarian Hyperstimulation: an adjunct to assisted reproductive technology. Fertil Steril 1994; 61:1158-60.

Royal College of Obstetricians and Gynecologists. Infertiltity: Guidelines for practice. London: RCOG, 1993.