Newsletter

Table of Contents

20.07.2004

Newsletter No. 28

Gynaecologic Endocrinology and Reproductive Medicine

Zygote transfer on day 1 versus cleavage stage embryo transfer on day 3: a prospective randomized trial.
Joseph Price oration. The multiple gestation epidemic: the role of the assisted reproductive technologies.
Single top quality embryo transfer as a model for prediction of early pregnancy outcome.
A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles.
Single embryo transfer - state of the art.

Reproductive Biology

On the frequency of intercourse around ovulation: evidence for biological influences.

1. Zygote transfer on day 1 versus cleavage stage embryo transfer on day 3: a prospective randomized trial.

It has been reported that pronuclear morphology is related to embryo quality and viability, and that zygote stage embryos might establish pregnancies after being transferred to the uterus. The objective of this study was to investigate whether transferring zygotes on day 1 would result in similar pregnancy rates compared to transferring cleavage stage embryos on day 3 in a prospective randomized trial. Patients undergoing IVF/ICSI treatments were randomized to either day 1 or day 3 transfers by envelope withdrawal technique. Zygotes were classified as 'pattern 0' and 'non-pattern 0' according to the size and alignment of pronuclei, the number and distribution of nucleoli. The two best zygotes or embryos were transferred on day 1 or day 3 respectively. The primary outcome measure was pregnancy rate. Pregnancy rates were higher in day 3 group (55/131, 42%) when compared to day 1 (34/123, 28%, P = 0.024). Similarly, implantation rates were higher in day 3 group (P = 0.03). There were more cycles with cryopreservation in the day 1 group (P < 0.001). Embryo quality on day 3 was similar between pattern 0 and non-pattern 0 zygotes. It is concluded that day 3 embryo transfers result in better pregnancy and implantation rates compared to day 1 zygote transfers. The present pronuclei scoring cannot reliably select zygotes for transfer on day 1.

Jaroudi K, Al-Hassan S, Sieck U, Al-Sufyan H, Al-Kabra M, Coskun S. Zygote transfer on day 1 versus cleavage stage embryo transfer on day 3: a prospective randomized trial. Hum Reprod. 2004 Mar;19(3):645-8. Epub 2004 Jan 29.

2. The multiple gestation epidemic: the role of the assisted reproductive technologies.

There can be no doubt that assisted reproduction techniques have brought joy and happiness to many patients and that this has provided immense satisfaction to many practitioners. However, the current inevitability of multiple births can no longer be accepted. For most patients, there is no reason to ever replace more than two embryos, and hence there should be no further risk of triplet births. All the evidence points to no disadvantage in the reduction in the number of embryos that are replaced in terms of pregnancy rates. Furthermore, twin pregnancies could be reduced considerably in number by the transfer of only 1 embryo on several occasions rather than several embryos on 1 occasion. It is likely that this approach will be adopted gradually in the coming years. Already many clinics in several countries are moving quickly in this direction. The duty of care for infertile couples should not be compromised by a headlong desire to achieve pregnancy at any cost. High-order multiple births are an unacceptable cost. The aim of treatment should be a singleton pregnancy and a normal healthy baby.

Templeton A. Joseph Price oration. The multiple gestation epidemic: the role of the assisted reproductive technologies. Am J Obstet Gynecol. 2004 Apr;190(4):894-8.

3. Single top quality embryo transfer as a model for prediction of early pregnancy outcome.

Single embryo transfer (particularly of a top quality embryo) is an excellent model to correlate embryo quality in terms of morphological criteria to early pregnancy. It was investigated whether this model could provide with more information on what happens after implantation in the first trimester of pregnancy. The outcome of 370 consecutive single top quality embryo transfers in patients younger than 38 years was analysed for pregnancy and first-trimester pregnancy loss (FTPL) before 13 weeks of gestation. Analysis was done on each cohort of embryos from which the transferred top quality embryo was selected. Serum HCG levels were measured on day 8 and day 12 after day 3 embryo transfer. The HCG index was calculated as the level of HCG on day 12/HCG on day 8. The pregnancy rate after single top quality embryo transfer was 51.9%. This was independent of the patients' age. FTPL, however, appeared to be age dependent: 15.4% for the whole group, 9% in patients younger than 30 years and 19% in patients above 30 years. The pregnancy rate was 50% in IVF cycles and 52% in ICSI cycles; FTPL was 19% in IVF cycles and 10% in ICSI cycles. Multiple regression analysis showed that these differences originated from age differences between both populations rather than from technique-related factors. An HCG level >or=45 IU/l on day 12 was predictive for ongoing pregnancy with 75.6% sensitivity and 100% specificity; an HCG index >or=3.5 similarly predicted ongoing pregnancy with 72.3% sensitivity and 100% specificity. These data show that embryo selection for transfer on day 3 can be used as an excellent tool for prediction of pregnancy but not for prediction of FTPL. The pregnancy rate of a single top quality embryo is not related to age, whereas FTPL is age dependent.

De Neubourg D, Gerris J, Mangelschots K, Van Royen E, Vercruyssen M, Elseviers M. Single top quality embryo transfer as a model for prediction of early pregnancy outcome. Hum Reprod. 2004 Jun;19(6):1476-9. Epub 2004 Apr 29.

4. A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles.

In this study the difference was analysed in maternal, neonatal and total costs after single (SET) versus double day 3 embryo transfer (DET). A two-centre prospective study was performed of women in their first IVF/ICSI cycle choosing between SET or DET. Infertility treatment data were gathered from a database; maternal and neonatal outcome data from a case report form (CRF); health economic data from medical acts registered in the CRF for the outpatient part and from hospital bills. SET was performed in 206/367 (56.1%) and DET in 161/367 (43.9%) women. In all, 367 transfers yielded 186 positive pregnancy tests, 148 ongoing pregnancies and 136 live deliveries (50.7, 40.3 and 37.1% per embryo transfer) of which 15 (11.0%) were twins. Live birth rate was 37.4% for SET, 36.6% for DET. Intention-to-treat analysis showed differences for: duration of pregnancy (SET: 39.0 +/- 1.4 versus DET: 38.3 +/- 2.2 weeks; P = 0.055), percentage prematurity (8.5 versus 23.8%; P = 0.033), percentage of neonates hospitalized (5.7 versus 17.9%; P = 0.121) and duration of neonatal hospitalization (6.3 +/- 2.2 versus 10.3 +/- 10.1 days; P = 0.01). Total cost after DET was higher (SET: 4700 +/- 3239 versus DET: 8613 +/- 10 105; P = 0.105), due to significantly higher neonatal costs (451 +/- 957 versus 3453 +/- 8154; P < 0.001) and not to differences in maternal costs (4250 +/- 2882 versus 5160 +/- 4106; P = 0.152). This prospective health economic study shows that transfer of a single top quality embryo is equally effective as, but substantially cheaper than, double embryo transfer in women <38 years of age in their first IVF/ICSI cycle.

Gerris J, De Sutter P, De Neubourg D, Van Royen E, Vander Elst J, Mangelschots K, Vercruyssen M, Kok P, Elseviers M, Annemans L, Pauwels P, Dhont M. A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles. Hum Reprod. 2004 Apr;19(4):917-23. Epub 2004 Feb 27.

5. Single embryo transfer - state of the art.

Every practitioner active in the field of assisted reproduction treatment is aware of the risks and complications related to twin and higher-order multiple pregnancies. Introduction of single embryo transfer (SET) into IVF/intracytoplasmic sperm injection (ICSI) is one of the possible ways of reducing the rate of twin pregnancy. Careful selection of patients, in combination with elective SET, has been shown to decrease the twin pregnancy rate while maintaining a stable ongoing pregnancy rate. The combination of a woman younger than 38 years of age, in her first or second IVF/ICSI cycle and with an embryo with a high implantation potential is the key to successful SET. This article will discuss embryo selection and patient selection and review the data published on SET. In the Centre for Reproductive Medicine at Middelheim Hospital, 39% of all transfers in 2002 were SET; the ongoing pregnancy rate remained stable at 30.6%. The twin (multiple) pregnancy rate declined to 11.7%. Particular attention should be drawn to the augmenting effect of the pregnancy rate of frozen-thawed cycles. Health economic data available so far subscribe the plea for SET.

De Neubourg D, Gerris J. Single embryo transfer - state of the art. Reprod Biomed Online. 2003 Dec;7(6):615-22.

6. On the frequency of intercourse around ovulation: evidence for biological influences.

Intercourse in mammals is often coordinated with ovulation, for example through fluctuations in libido or by the acceleration of ovulation with intercourse. Such coordination has not been established in humans. This possibility is explored by examining patterns of sexual intercourse in relation to ovulation. Sixty-eight sexually active North Carolina women with either an intrauterine device or tubal ligation provided data for up to three menstrual cycles. These women collected daily urine specimens and kept daily diaries of intercourse and menstrual bleeding. Major estrogen and progesterone metabolites excreted in urine were used to identify the day of ovulation. The fertile days of the cycle were defined as the 6 consecutive days ending with ovulation. Women contributed a total of 171 ovulatory cycles. Menstrual bleeding days were excluded from analysis. The frequency of intercourse rose during the follicular phase, peaking at ovulation and declining abruptly thereafter. The 6 consecutive days with most frequent intercourse corresponded with the 6 fertile days of the menstrual cycle. Intercourse was 24% more frequent during the 6 fertile days than during the remaining non-bleeding days (P < 0.001). It is concluded that there are apparently biological factors that promote intercourse during a woman's 6 fertile days.

Wilcox AJ, Baird DD, Dunson DB, McConnaughey DR, Kesner JS, Weinberg CR. On the frequency of intercourse around ovulation: evidence for biological influences. Hum Reprod. 2004 Jul;19(7):1539-43. Epub 2004 Jun 09.

Gerhard Leyendecker