Newsletter

Table of Contents

15.05.2001

Newsletter No. 9

Varicocele treatment
Blastocyst transfer: Open questions
IVF/ICSI: Avoidance of twin pregnancy. Towards the transfer of a single embryo
Aromatase inhibitor for induction of ovulation following clomiphene failure.

1. Varicocele treatment

Treatment of varicoceles became the most common treatment for male infertility merely on an empirical basis. However, in the age of evidence-based medicine it is surprising that only a few, and mainly recent, randomised controlled clinical trials with relevant outcome parameters have been published to allow adequate judgement of treatment effectiveness. Moreover, difficulties in study design could also be detected in most of these high-quality studies. Despite these difficulties and in contrast to the majority of uncontrolled studies on varicocelectomy, meta-analysis of these randomised controlled clinical studies involving 385 patients showed no significant treatment benefit and questions the common practice of varicocelectomy. Even the high-quality studies show conflicting results and therefore the topic of varicocele treatment will remain controversial and further randomised clinical trials should readdress this issue. For the time being, intervention by surgical or angiographic occlusion of the spermatic vein cannot be recommended

There is probably no subject that is more controversial in the area of male infertility than varicocele. The overwhelming majority of non-urologist infertility specialists in the world are extremely sceptical of the role of varicocele or varicocelectomy in the treatment of male infertility. Directors of most assisted reproductive technologies (ART) programmes view the enthusiasm with which urologists approach varicocelectomy as a potential impediment to the couple that is getting older and do not have much time left to become pregnant using ART.

Kamischke A, Nieschlag E (2001) Varicocele treatment in the light of evidence-based andrology. Hum. Reprod. Update 7: 65-69

Silber SJ (2001)The varicocele dilemma. Hum. Reprod. Update 7: 70-77

2. Blastocyst transfer: Open questions

Blastocyst transfer has been suggested to improve implantation rate without affecting pregnancy rate. It was the aim of a study to compare the pregnancy and implantation rates of day 3 and 5 transfers in a prospective randomised manner. Patients with four or more zygotes were randomly allocated on day 1 to either day 3 or 5 transfers. Fertilization was achieved through regular IVF or intracytoplasmic sperm injection (ICSI). Zygotes were kept in Medicult IVF medium for day 3 transfers and transferred into G1.2 and G2.2 on day 1 and 3 respectively for day 5 transfers. The morphologically best two or three embryos or blastocysts were chosen for transfer in both groups. Overall pregnancy rates per embryo transfer were the same (39%) in day 3 and 5 transfers. Implantation rates were 21 and 24% for day 3 and 5 transfers respectively. The pregnancy and implantation rates for day 5 transfers were significantly affected by the availability of at least one blastocyst to transfer and the number of zygotes. The number of good quality embryos on day 3 also significantly affected pregnancy and implantation rates on day 5 transfers. Multiple gestation rate, number of abortions and ongoing pregnancies were similar in both groups. Day 3 and 5 transfer had similar pregnancy, implantation and twinning rates. Thus, currently, day 5 transfers have no advantages over day 3 transfers. Blastocysts are regarded as having increased implantation potential, and two blastocysts are typically transferred, which reduces the occurrence of high order multiple gestations. However, with current techniques, most cleavage embryos do not become blastocysts and it is not clear how many of these embryos would have implanted had they been replaced at the cleavage stage. Furthermore, experience with blastocyst cryopreservation is lacking and the overall benefit of blastocyst culture is unknown, unless we consider the combined pregnancy rates of both fresh and frozen blastocysts.

Coskun S, Hollanders J, Al-Hassan S, Al-Sufyan H, Al-Mayman H, Jaroudi K (2000) Day 5 versus day 3 embryo transfer: a controlled randomised trial. Hum Reprod. 15: 1947-1952

Alper MM, Brinsden P, Fischer R, Wikland M (2001) To blastocyst or not to blastocyst? That is the question. Hum. Reprod. 16: 617-619

3. IVF/ICSI: Avoidance of twin pregnancy. Towards the transfer of a single embryo

Multiple and also twin pregnancies constitute the most serious complication for both mother and children after IVF/ICSI treatment, but transfer of at least two 'best looking' embryos remains the standard policy. Some centres now electively transfer a single embryo (eSET) when particular embryo quality and patient criteria are met. Results from several centres were presented during an ESHRE Campus Course, held on May 6, 2000. Sound clinical trials are needed to clarify several points of discussion. What is the clinical profile of patients in whom eSET should be considered? Will the overall (ongoing) pregnancy rate of the IVF/ICSI programme decrease if eSET is performed in these patients? What is the twinning rate when eSET is a routine policy? Will the financial gain by avoiding perinatal hospitalisation costs of prevented twins be balanced by the likely need to perform a number of extra IVF/ICSI cycles? What will be gained by freezing the extra number of high quality embryos? Should eSET be performed at the 2 pronuclear stage, the early cleaving embryo or the blastocyst stage? Clinical evidence is accumulating that by proper selection of the patients and the embryo to be transferred pregnancy rates per treatment cycle can be achieved that compare well with the normal conception rate per cycle. Thus, common sense dictates that eSET as a concept should be applied from now onwards.

ESHRE Campus Course Report (2001) Prevention of twin pregnancies after IVF/ICSI by single embryo transfer. 16: 790-800

4. Aromatase inhibitor for induction of ovulation following clomiphene failure.

To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful a prospective trial in infertility patients was performed. Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm were treated with the aromatase inhibitor letrozole orally in a dose of 2.5 mg on days 3-7 after menses. With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%). Thus, oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavourable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.

Mitwally MFM, Casper RF (2001) Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fert. Steril. 75: 305-309

Gerhard Leyendecker