© Springer India 2015
Gautam N. Allahbadia and Claudio F. Chillik (eds.)Human Embryo Transfer10.1007/978-81-322-1115-0_1010. Is There A Role for Tubal Transfers?
(1)
Reproductive Endocrinologist and Infertility Specialist, Fakih IVF Fertility Center, Abu Dhabi and Dubai, UAE
(2)
Fakih IVF Fertility Center, Abu Dhabi and Dubai, UAE
(3)
IVF Michigan Fertility Center, Michigan, MI, USA
(4)
Al-Shunnar Polyclinic, Fakih IVF Fertility Center, Dubai, UAE
Abstract
Tubal transfers were a forgotten entity due to development of culture media, laboratory conditions and other advances in laboratory techniques including the advent of intracytoplasmic sperm injection (ICSI). There is resurgence of interest in this modality as a means to bypass technical and mechanical difficulties during uterine embryo transfers and in dealing with the uterine embryo transfers facing high-order recurrent failures. In the last and most common indication, the tubal transfer of embryos or zygote intra-fallopian transfer may enhance the implantation rates and pregnancy rates by providing a more conducive physiologic environment, emphasizing the role of Fallopian tube in embryogenesis and its development, by improving the synchrony of the endometrium and embryo development, bypassing the junctional contractions, which are inevitable, even in the most atraumatic uterine embryo transfers and playing a role in embryo expulsion. The logistics, cost, risks of laparoscopy and slightly increased risk of ectopic pregnancy may hinder its frequent application but may be a saving grace for high-order recurrent failures where extensive investigations reveal nothing. It has been performed most often for cleavage-stage embryos (day 1–3), both fresh and cryopreserved embryos, though blastocyst intra-fallopian transfer has also successfully achieved intrauterine pregnancy.
Keywords
Tubal transferRecurrent implantation failureGamete intra-fallopian transferZygote intra-fallopian transferLaparoscopic transferEmbryo transferIntroduction
The ability of tubal transfer of an embryo to produce pregnancy and live birth was first demonstrated in a non-human primate model in 1984 [1]. Two years later the first successful micro-laparoscopic intra-fallopian transfer in humans was demonstrated [2].
Clinical experience with the transcervical uterine embryo transfer (UET) shows that it is a relatively simple technique and has been the most common route of transfer. It does not entail risk of anaesthesia and laparoscopy [3], and its cost-effectiveness has been proven time and again. It allows the selection of the best embryo after 2–5 days of culture and is a widely practised procedure requiring training with a short learning curve.
Transcervical embryo transfer is far from perfect though. Experimental studies with mock ET have shown expulsion of methylene blue in 57 % of transfers [4] and movement of roentgenogram contrast medium towards the Fallopian tubes, cervix and/or vagina in 38.2 %, 8.8 % and 11.8 % transfers, respectively [5].
Back to Nature with Tubal Embryo Transfers (TET) or Zygote Intra-fallopian Transfer (ZIFT)
The resurgence of interest in tubal embryo transfers has been due to recurrent failures with uterine embryo transfer or technical difficulties encountered in it. The first pregnancy from ZIFT was reported in 1986 as a modification of gamete intra-fallopian transfer (GIFT). It was meant to treat patients with male factor infertility or failed GIFT procedure but was extended to cover other aetiologies [2].
ZIFT was a much popular technique in the early days of IVF, and subsequently, with the major advances in culture media, laboratory conditions and development of ICSI, its use has declined due to physical burden, logistics and costs involved [8]. The understanding of the mechanism of superiority of ZIFT over standard UET is fragmentary and incomplete.
The conduit that the Fallopian tube is anatomically thought to be is much more than a passive passage for gametes and embryos. It is an active channel, which participates in several significant functions which are dynamic, like muscular contractions and metabolism, as well as chemokine production [9]. It is a major contributor to the process of fertilization and early embryogenesis.
The use of in vitro fertilization (IVF) enables the bypassing of tubes but fails to create the same tubal microenvironment for the initial stages of embryo development in the laboratory. It may be argued that tubal transfer of zygotes and early embryos is more physiological and creates an environment more conducive for this and hence, results in higher implantation and pregnancy rates [2]. The transfer of zygotes to the Fallopian tubes allows for the early cleavage and development in the natural and physiological environment of the Fallopian tube with the presence of natural cytokines and growth factors, which may enhance implantation. The tubal environment will be potentially superior to the artificial culture media and incubators [10].
Avoidance of poor in vitro culture media is unlikely to be the major mechanism involved in the successful outcome of ZIFT. It may be more likely related to mechanical aspects of the procedure.
A better synchronization between embryonic development and endometrial development is highly apparent with this transfer, with the advantage of avoidance of potential traumatic insertion of catheters. It is well known that functional contractions on the day of transfer are associated with a reduced pregnancy rate [11].
Routine procedures and, more often, difficult cervical transfers produce strong junctional waves and contractions in the fundal area which may then migrate to the cervix, affect the retention of the embryos in the favourable endometrial environment and promote expulsion. Easy transfers will not affect the pattern of contractions to that extent. Hence, mechanical factors due to the catheter stimulation may play a significant role in the implantation process.
Indications for ZIFT
Most retrospective studies show increased pregnancy rates with ZIFT [14, 15]. Many non-randomized studies have also reported higher pregnancy rates for tubal transfer of embryos (ZIFT) than for intrauterine embryo transfer (ET) [16, 17]. In contrast, other studies show comparable rates between the two procedures [18, 19]. The largest uncontrolled study, the SART registry, has consistently shown higher pregnancy rates with tubal transfers than uterine transfers in the past decade. The clinical pregnancy rate per retrieval (37.5 % versus 31.1 %) and per transfer (40.1 % versus 33.3 %) remains higher for ZIFT in this non-randomized database [20]. In the following sections, we will discuss each of the indications.
Recurrent Implantation Failure (RIF)
Recurrent implantation failure presents a major challenge for the medical team [21, 22]. The pathophysiology of RIF should be intensely investigated to allow the application of therapeutic or modifying measures during the course of initiation of treatment of the next cycle. The pregnancy rates do not change over the first four attempts but drop by 40 % in subsequent cycles in IVF failures [9]. There are multiple therapeutic approaches, which have been tried in these patients like laser-assisted hatching, embryo co-culture, blastocyst transfer, aneuploidy screening by preimplantation diagnosis and salpingectomy for hydrosalpinges [8]. None of them have been found to be consistent and promising. Some of them are technically tedious, and some do not have evidence from randomized trials of being statistically significant to success. Cruz et al. [23], in a retrospective study on RIF patients, reported enhanced success with blastocyst transfer, with a increase in implantation and pregnancy rates as compared to conventional day 3 transfers.
However, in a prospective study comparing the blastocyst transfer versus ZIFT in patients with recurrent implantation failure, highly favourable clinical pregnancy and live birth rates, all in the range of 40 %, emphasized the role of ZIFT as a powerful clinical tool for these patients. The extended culture and transfer at the blastocyst stage failed to increase the implantation or improve prognosis for patients with RIF [24].
A retrospective cohort study was performed at a tertiary referral university hospital in Israel, where a group of patients with approximately 8.1 previous cycles underwent 280 ZIFT procedures. The live birth rate of patients was 39.8 %, which is remarkable considering the poor prognosis associated with RIF. They concluded that ZIFT remains an important modality in the management of high-order RIF and is possible with at least one unobstructed tube in such patients [25].
Aslan et al. [26] analyzed 141 ZIFT cycles among 132 patients with RIF and compared them with 145 UET cycles amongst 97 RIF patients. The implantation rates, clinical pregnancy rates and live birth rates were comparable in both groups. The clinical pregnancy rate was found to be 22.7 % [26].
The authors’ experience with ZIFT is a series of 32 cases from January 2011 to April 2013, which resulted in a clinical pregnancy rate of 37.5 %. The most common indication was recurrent implantation failure. There were three cases with cervical stenosis and scarring due to previous cervical surgeries (cone biopsy and large loop excision of the transformation zone). The number of previous failures was 4.6 ± 2.5, and no ectopic pregnancy was found in this series so far [27].
Tubal Factor Infertility
Farhi et al. [28] performed zygote intra-fallopian transfers in patients for the first time with mild tubal factor infertility without hydrosalpinges. Patients with tubal factor but at least one patent tube proven on HSG or laparoscopy, with at least four previous implantation failures after IVF-ET in which at least three embryos were replaced per transfer, were included. Four to six zygotes were transferred by laparoscopy 24–48 h after retrieval. In the 112 cycles, the pregnancy rates and implantation rates were 35.1 % and 11.1 % respectively. Similar rates were present in both tubal and non-tubal factor patients. There was an ectopic pregnancy rate of 2.5 %. The pregnancy and implantation rates in IVF-transcervical ET were 6.9 % and 2.5 %, which was significantly lower. The ZIFT procedure was performed only in patients who had a fertilization rate of >60 %, who produced four or more zygotes in the ZIFT cycle and who had an endometrial thickness of ≥7 mm on the day of human chorionic administration (hCG) administration. If hydrosalpinges are present, salpingectomy is the best way forward [28].
A comparative study between combined GIFT/IVF and ZIFT /IVF was performed for unexplained infertility, anovulation and male factor facing recurrent IVF failures. Both resulted in similar pregnancy, delivery, implantation and multiple gestation rates [29].
Non-tubal Factor Infertility
A prospective randomized study from Iran randomized patients with normal hysterosalpingograms and/or normal laparoscopy and those who had easy mock transfers to be randomized for ZIFT and UET. The patients with RIF with contraindications to laparoscopy, azoospermia and difficult mock ETs were excluded. The study showed a clinical pregnancy rate per transfer of 42.1 % following ZIFT and 21 % following UET. The ongoing pregnancy rates were 35.3 % following ZIFT versus 20 % following UET [3].
The reported pregnancy rate per transfer was 47.7 % for IVF and 37.9 % for ZIFT in a study by Tanbo et al. [30] which included couples with unexplained infertility, peritoneal endometriosis or reduced semen quality [30].
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