Delivery rates following IVF treatment, using two recombinant FSH preparations for ovarian stimulation

BACKGROUND: A prospective, semi-randomized, open, clinical study was conducted to compare ovarian response, pregnancy outcome and delivery rates using two recombinant FSH preparations (Gonal-F and Puregon) for IVF. METHODS: We analysed stimulation parameters and outcome data in 812 initiated treatment cycles where 292 women used Gonal-F and 200 used Puregon. Embryo transfer was carried out in 676 cycles. In the two preparation groups we also compared 170 women previously treated with FSH for IVF with 266 previously untreated. RESULTS: The pregnancy rate with Gonal-F was 26% and with Puregon 28%. Delivery rates were identical, 22%. Clinical pregnancy and delivery rates per cycle with embryo transfer in earlier untreated women were 29.0 and 24.0%, whereas in previously treated women they were 23.5 and 18.8% respectively. After repeated cycles, delivery frequencies consecutively decreased, independent of the FSH preparation used. CONCLUSION: Gonal-F and Puregon seem to be equally potent in achieving follicular development and equally effective, in terms of delivery rates, for use in an IVF programme. Repeated cycles resulted in equally large consecutive decreases in delivery rates, regardless of preparation choice, but were considered worthwhile for up to three stimulation cycles in selected patients.     

A prospective, randomized comparison of two starting doses of recombinant FSH in combination with cetrorelix in women undergoing ovarian stimulation for IVF/ICSI

BACKGROUND: A prospective randomized study was carried out in two centres to compare the number of oocytes retrieved after two different starting doses of recombinant human FSH (rhFSH) (Gonal-F) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI) cycles using the multiple dose regimen of the gonadotrophin-releasing hormone (GnRH) antagonist cetrorelix (Cetrotide) to prevent induction of the premature LH surge. METHODS: Sixty women were randomized to receive rhFSH 150 IU ('low'), and 60 women to receive rhFSH 225 IU ('high') as the starting dose for the first 5 days of stimulation. From stimulation day 6 and onwards, including the day of human chorionic gonadotrophin (HCG) administration, the women received 0.25 mg of cetrorelix as a daily dose. The primary endpoint was the number of oocytes retrieved. RESULTS: The mean number (+/- SD) of oocytes was 9.1 +/- 4.4 and 11.0 +/- 4.6 in the 'low' and 'high' groups respectively (P = 0.024). The mean number of 75 IU ampoules of rhFSH was significantly lower in the 'low' group (23.0 +/- 6.3 versus 30.5 +/- 5.6, P < 0.0001). The ongoing pregnancy rate per started cycle and per embryo transfer were 25.9 and 28.8% versus 25.4 and 26.8% respectively in the 'low' and 'high' rhFSH groups (P = NS). CONCLUSIONS: When using a starting dose of 225 IU rhFSH combined with the multiple dose of 0.25 mg cetrorelix from stimulation day 6, significantly more oocytes were obtained than with a starting dose of 150 IU rhFSH.     

Elective transfer of one embryo results in an acceptable pregnancy rate and eliminates the risk of multiple birth.

To avoid multiple pregnancies without compromising pregnancy rates (PR) is a challenge in assisted reproduction. We have compared pregnancy results among 74 elective one-embryo transfers (group 2) and 94 transfers where only one embryo was available (group 1). All the fresh embryo cycles during 1997 in two clinics in Helsinki were analysed, and cumulative PR among these couples after frozen-thawed embryo transfers up to June 1998 were counted. In group 2, where at least two embryos were available for transfer, and only one was transferred on day 2 or 3, the PR per embryo transfer was 29.7%. In group 1, the PR per embryo transfer was 20.2%. In group 2, the cumulative PR after frozen-thawed embryo transfers was 47.3% per oocyte retrieval. Over the same time, 742 two-embryo transfers were carried out. The PR per embryo transfer was 29.4% in these subjects, but 23.9% of these pregnancies were twins. The implantation rates, as well as the PR, were highest when the embryos were at the four- to five-cell stage on day 2 (35.8 versus 9.7% compared with the two- to three-cell stage, P < 0.001) or at the six- to eight-cell stage on day 3 (45.5%). The PR per embryo transfer was higher when a grade 1 or 2 embryo was transferred compared with a grade three embryo (34. 0 and 26.7% versus 8.8% respectively, P < 0.05). In women 35 years or younger, the PR per elective one-embryo transfer was 32.8%. The corresponding figure in women older than 35 years was 18.8%. On the basis of these results, elective one-embryo transfer can be highly recommended, at least in subjects who are younger than 35 years of age, and who have grade one or grade two embryos available for transfer.     

Recombinant follicle stimulating hormone in in-vitro fertilization treatment-clinical experience with follitropin alpha and follitropin beta

The objective of this prospective study was to compare the outcome of ovarian hyperstimulation for in-vitro fertilization (IVF) using two different preparations of recombinant follicle stimulating hormone (FSH). The study was based on 296 consecutive IVF cycles in 1997, 199 performed using follitropin alpha (Gonal-F) and 97 performed using follitropin beta (Puregon). Outcome was compared regarding pregnancy rate, oestradiol and progesterone response, endometrial thickness, follicle number, number of retrieved oocytes, fertilized oocytes, sperm count and sperm motility. There was no significant difference in outcome of stimulation. Clinical pregnancy rate was similar, 29.1% for Gonal-F and 28.1% for Puregon. There was no difference in endometrial response, oestradiol response, number of smaller (12-15 mm) or larger (>15 mm) follicles, number of oocytes retrieved, fertilized, divided and replaced, in sperm counts or in sperm progressive motility. There was a lower follicle number in the Puregon group, but not statistically significant. The serum progesterone concentrations on the day of oocyte retrieval, however, were significantly lower in the Puregon group. In conclusion, it was not possible to find significant differences in the IVF programme with regard to stimulation outcome between Gonal-F and Puregon. The results of this study indicate that Gonal-F and Puregon may be equally suitable for use in ovarian stimulation for IVF.     

A prospective randomized study: day 2 versus day 5 embryo transfer

BACKGROUND: This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers. METHODS: Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred. RESULTS: The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%). CONCLUSION: This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers.     

Encouraging results despite complexity of multidisciplinary care of HIV-infected women using assisted reproduction techniques

BACKGROUND: Assisted reproduction technologies can treat infertility for human immunodeficiency virus (HIV) seropositive women. We assessed the efficacy of these techniques in the results and difficulties encountered while conducting our assisted reproduction programme for 49 couples in which at least the woman had HIV infection that was currently under control. METHODS: Treatments included intrauterine insemination (IUI), IVF and ICSI, with ovarian stimulation. Embryos were transferred on day 3 after oocyte retrieval. An elective single transfer was performed, except for patients aged > or = 40 years. RESULTS: The median age of the women was 36 years. Ten IUI, nine IVF, 53 ICSI and 10 frozen-thawed embryo transfers have been performed. No pregnancy occurred following the IUI trials but for the couples with IVF and ICSI attempts the clinical pregnancy rate per embryo transfer was 23.9%. Eight babies have been born leading to a 22.2% take home baby rate per treated couple. Contamination was not observed in any newborn. CONCLUSIONS: Assisted reproduction technologies and particularly ICSI can provide HIV seropositive women with a safe means of mothering children. Results are encouraging when considering the age of the patients and a preferential single embryo transfer.     

Frozen embryo transfers: implications of clinical and embryological factors on the pregnancy outcome

BACKGROUND: Frozen embryo transfers are characterized by impaired pregnancy outcome and increased incidence of pregnancy loss as compared with fresh IVF/ICSI embryo transfers. In this study, we performed a retrospective analysis of clinical and embryological factors that potentially influence the outcome of frozen embryo transfer. METHODS: We reviewed the outcome of 1242 frozen embryo transfers with respect to the age of the woman, the method of fertilization, embryo quality before and after freezing and the number of embryos transferred. RESULTS AND CONCLUSIONS: The pregnancy (positive hCG) and clinical pregnancy rates were 25.8 and 21.1%, respectively. A total of 107 (33.3%) of the 321 pregnancies identified by a positive hCG test miscarried either before (18.4%) or after (15%) the clinical recognition of gestational sac(s). The delivery rate for the frozen embryo transfers analysed was 17.2%. Our data revealed that the delivery rate after frozen embryo transfer was dependent on both the woman's age and the quality of embryos transferred, at the same time being unaffected by IVF/ICSI treatment. In addition, the increased woman's age at IVF/ICSI treatment was identified as the only parameter elevating the biochemical pregnancy rate, whereas the clinical abortion rate was found to be unrelated to the clinical or embryological parameters studied.     

Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial.

A prospective randomized study comparing single embryo transfer with double embryo transfer after in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) was carried out. First, top quality embryo characteristics were delineated by retrospectively analysing embryos resulting in ongoing twins after double embryo transfer. A top quality embryo was characterized by the presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after insemination, the absence of multinucleated blastomeres and <20% cellular fragments on day 2 and day 3 after fertilization. Using these criteria, a prospective study was conducted in women <34 years of age, who started their first IVF/ICSI cycle. Of 194 eligible patients, 110 agreed to participate of whom 53 produced at least two top quality embryos and were prospectively randomized. In all, 26 single embryo transfers resulted in 17 conceptions, 14 clinical and 10 ongoing pregnancies [implantation rate (IR) = 42.3%; ongoing pregnancy rate (OPR) = 38.5%] with one monozygotic twin; 27 double embryo transfers resulted in 20 ongoing conceptions with six (30%) twins (IR = 48.1%; OPR = 74%). We conclude that by using single embryo transfer and strict embryo criteria, an OPR similar to that in normal fertile couples can be achieved after IVF/ICSI, while limiting the dizygotic twin pregnancy rate to its natural incidence of <1% of all ongoing pregnancies.     

Day 2 elective single embryo transfer in clinical practice: better outcome in ICSI cycles

BACKGROUND: Single embryo transfer (SET) after IVF/ICSI has been shown to result in an acceptable pregnancy rate in selected subjects. In our unit, SET is routinely carried out among women under the age of 36 in the first or second treatment cycle when a top-quality embryo is available. In order to define further the selection criteria for SET, we have analysed the outcome of elective SET (eSET), including the cumulative pregnancy rate after frozen embryo transfers, performed in the years 2000-2002 in the Oulu Fertility Center. METHODS: During the study period, a total of 1271 transfers were performed, and in 468 cycles SET (39% of all transfers) was carried out. Of the SET cycles, in 308 cases a top-quality embryo was transferred on day 2 and extra embryos were frozen. Of these eSET cycles, ICSI was carried out in 87 cycles (28%). RESULTS: The overall clinical pregnancy rate per transfer was 34.7% in the eSET cycles. In the eSET ICSI cycles, the clinical pregnancy rate was significantly higher than in the corresponding IVF cycles (50.6 versus 28.5%, P < 0.001). The cumulative pregnancy rate per patient after fresh and frozen embryo transfers was also significantly higher after ICSI (71.2 versus 53.4%, P < 0.01). CONCLUSIONS: A high cumulative pregnancy rate per oocyte retrieval can be achieved after eSET in daily clinical practice. The implantation rate of fresh top-quality embryos in the ICSI cycles was significantly higher than in the IVF cycles, possibly due to more successful selection of the embryo for embryo transfer on day 2 after ICSI. In addition, our data suggest that embryo quality is a more important determinant of outcome than the age of the woman.     

One year's experience with elective transfer of two good quality embryos in the human in-vitro fertilization and intracytoplasmic sperm injection programmes

High incidences of multiple pregnancies, after transferringa maximum of three embryos, were observed after in-vitro fertilization(IVF) treatment. In a randomized study, it was demonstratedthat, after taking into account embryo quality and other positivelyinterfering parameters, an elective transfer of two good qualityembryos does not significantly influence the pregnancy rate.The intracytoplasmic sperm injection (ICSI) technique was successfullydeveloped in the meantime and high incidences of multiple pregnancieswere also obtained after ICSI. The question arose whether afterICSI there was also room for elective double embryo transferin a well-defined patient group. This report covers 1 year of IVF and ICSI treatment and theresults are presented in relation to the number of embryos transferred.The embryo development is similar for zygotes obtained afterIVF and ICSI; for both techniques 63% of the zygotes developto type A-B embryos and 13% to type C embryos. There is alsono difference in the pregnancy rate after ICSI or IVF. Globally,after IVF, 307 out of the 766 double and triple transfers (40.1%)and 317 out of 774 double and triple transfers (40.9%) afterICSI resulted in a positive HCG. After IVF, 73.9% (227) andafter ICSI 76.3% (242) of the pregnancies were evolutive. Neitherwas there any difference between the two techniques as regardsthe implantation rate per transferred embryo. After IVF, 22.8%of the transferred embryos implanted compared with 21.8% afterICSI. When the elective double embryo transfers were compared,no difference was found between IVF and ICSI. After IVF, 102of the 211 elective double transfers (48.1%) resulted in a pregnancyversus 93 out of 225 (41.3%) after ICSI [not significant (NS)].A high implantation rate per transferred embryo (IVF: 33.2%;ICSI: 26.9%, NS) was obtained in this elective double transfercategory, as was also reported in the randomized study. Thesedata confirm the results obtained in our randomized study andthe effectiveness of the elective double embryo transfer forIVF as well as for ICSI.     

Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH. On behalf of The Feronia and Apis study group

This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F) with highly purified urinary human FSH (uhFSH, Metrodin HP) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F or Metrodin HP, at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F and Metrodin HP groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F than with Metrodin HP (11.6 +/- 1.9 days versus 12. 4 +/- 2.7 days; P < 0.0001) and significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/- 5.1, P < 0.0002). There were, however, significantly more follicles > or =10 mm in diameter with Gonal-F (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P < 0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F had a higher pregnancy rate per cycle than patients given Metrodin HP (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F and Metrodin HP patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F is clearly more effective than Metrodin HP in inducing multifollicular development.     

A biological, immunological and physico-chemical comparison of the current clinical batches of the recombinant FSH preparations Gonal-F and Puregon

The immunopotency and in-vitro biopotency of clinical batches of Gonal-F((R)) and Puregon((R)) (recombinant human follicle stimulating hormones) were compared and their carbohydrate chains investigated for charge heterogeneity and internal carbohydrate complexity. Immunopotency (IU/pmol) for both Gonal-F and Puregon was 0.35 +/- 0.01 and biopotency (ED(50), pmol/l) was similar, being 7.3 +/- 0.6 and 5.4 +/- 0.2 respectively. Charge distributions were essentially the same with no difference either in median isoelectric point (pI) (between 4.26 and 4.50), or in the bulk of material fractionated between pI 4 and 5 (66.0 +/- 1.8% Gonal-F and 72.0 +/- 1.8% Puregon). However, there were minor differences in charge at extremes of pI, Gonal-F being slightly more acidic: 18.2% Gonal-F versus 9.8% Puregon at pI 3.5-4.0 (P: = 0.03) and 6.7% Gonal-F versus 10.7% Puregon at pI 5.0-5.5 (P: = 0.03). Carbohydrate complexity was the same: 9.3 versus 10.9 (complex), 76.6 versus 78.6 (intermediate) and 14.1 versus 10.5% (simple). In summary, Gonal-F and Puregon have similar immunopotency, in-vitro biopotency and internal carbohydrate complexity, differing slightly in charge heterogeneity, Gonal-F having more acidic glycoforms. We conclude them to be intrinsically very similar, expecting no difference in clinical efficacy on the basis of respective structure.     

Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): a pilot study with minimal stimulation

Natural cycles were abandoned in in-vitro fertilization (IVF) embryo transfer, due to premature luteinizing hormone (LH) surges--and subsequent high cancellation rates. In this study, we investigated the administration of a new gonadotrophin-releasing hormone antagonist (Cetrorelix) in the late follicular phase of natural cycles in patients undergoing IVF and intracytoplasmic sperm injection (ICSI). A total of 44 cycles from 33 healthy women [mean age 34.1 +/- 1.4 (range 26-36) years] were monitored, starting on day 8 by daily ultrasound and measurement of serum concentrations of oestradiol, LH, follicle stimulating hormone (FSH) and progesterone. When plasma oestradiol concentrations reached 100-150 pg/ml, with a lead follicle between 12-14 mm diameter, a single injection (s.c.) of 0.5 mg (19 cycles) or 1 mg (25 cycles) Cetrorelix was administered. Human menopausal gonadotrophin (HMG; 150 IU) was administered daily at the time of the first injection of Cetrorelix, and repeated thereafter until human chorionic gonadotrophin (HCG) administration. Four out of 44 cycles were cancelled (9.0%). No decline in follicular growth or oestradiol secretion was observed after Cetrorelix administration. A total of 40 oocyte retrievals leading to 22 transfers (55%) was performed. In 10 cycles (25%), no oocyte was obtained. Fertilization failure despite ICSI occurred in six cycles (15%). In two patients the embryo was arrested at the 2 pronuclear (PN) stage. The stimulation was minimal (4.7 +/- 1.4 HMG ampoules). A total of seven clinical pregnancies was obtained (32.0% per transfer, 17.5% per retrieval), of which five are ongoing. Thus, a spontaneous cycle and the GnRH antagonist Cetrorelix in single dose administration could represent a first-choice IVF treatment with none of the complications and risks of current controlled ovarian hyperstimulation protocols, and an acceptable success rate.     

Ratio of oestradiol concentration on the day of human chorionic gonadotrophin administration to mid-luteal oestradiol concentration is predictive of in-vitro fertilization outcome.

The role of luteal oestradiol for successful implantation in humans seems to be permissive rather than obligatory. Few studies have attempted to clarify the role of early luteal oestradiol in in-vitro fertilization (IVF) outcome, whether peri-implantation oestradiol is predictive of successful IVF outcome. We retrospectively analysed 106 women undergoing 106 IVF/embryo transfer cycles. Only the first treatment cycle per patient was analysed. Peak oestradiol denoted the concentration on the day of human chorionic gonadotrophin (HCG) administration. Mid-luteal oestradiol was obtained 3 days after embryo transfer (8 days after HCG administration). A total of 44 pregnancies were noted (41.51%). There were no differences in age, cycle day 3 follicle stimulating hormone (FSH), peak oestradiol, number of retrieved oocytes, number of embryo transfers, and mid-luteal oestradiol between pregnant and non-pregnant women. However, the ratio of day of HCG oestradiol to mid-luteal oestradiol was highly predictive of successful outcome: the ongoing pregnancy rate and implantation rate (sacs with fetal heart beat/embryo transfer) were 15.8 and 5.7% respectively if the above ratio exceeded 5.0 (n = 19), compared to 42.1 and 16.3%, and 53.3 and 26. 5% if the ratio was between 0.4 and 2.5 (n = 57), and between 2.5 and 5.0 (n = 30) respectively. Our study suggests that the magnitude of decline in oestradiol concentrations after oocyte retrieval may be important in predicting IVF success. We postulate that endometrial integrity may become compromised when a dramatic drop in oestradiol occurs by the mid-luteal period. Whether these women benefit from oestradiol supplementation after oocyte retrieval remains to be investigated.     

Effect of endometriosis on IVF/ICSI outcome: stage III/IV endometriosis worsens cumulative pregnancy and live-born rates

BACKGROUND: Women with endometriosis often need IVF to conceive-most women need several cycles of treatment. METHODS: To evaluate the impact of moderate to severe endometriosis on cumulative IVF outcome, we carried out an observational study on 98 consecutive women who underwent IVF or ICSI treatment and had endometriosis diagnosed by laparoscopy or laparotomy and classified as minimal to mild endometriosis (American Society for Reproductive Medicine I/II) (n = 31) or moderate to severe endometriosis (American Society for Reproductive Medicine III/IV) (n = 67). The reference group consisted of 87 consecutive women with tubal infertility. The main outcome measures were cumulative pregnancy and live birth rates. RESULTS: There was a significantly lower pregnancy rate per fresh embryo transfer after pooled cycles (1-4) among women with stage III/IV endometriosis (22.6%) compared to stage I/II group (40.0%) or tubal infertility (36.6%). After 1-4 IVF/ICSI treatments, including frozen embryo transfer, 56.7% of the women with stage III/IV endometriosis were pregnant and 40.3% gave birth. The corresponding values were 67.7/55.8% when endometriosis was stage I/II and 81.6/43.7% in the controls respectively. CONCLUSION: Stage III/IV endometriosis means a worse prognosis for IVF/ICSI treatments compared to milder stages or tubal factors. Lower implantation and multiple pregnancy rates offer some support to our practice to continue two embryo transfers in this group.     

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

BACKGROUND: 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. We investigated whether this model could provide us with more information on what happens after implantation in the first trimester of pregnancy. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

A relative reduction in mid-follicular LH concentrations during GnRH agonist IVF/ICSI cycles leads to lower live birth rates

BACKGROUND: The effect of early- and mid-follicular LH concentrations on the ovarian response and pregnancy outcomes was evaluated in women receiving pituitary down-regulation with a GnRH agonist and ovarian stimulation with recombinant FSH (rFSH) during IVF/ICSI treatment. METHODS: Blood samples were collected prospectively from 701 cycles (560 patients) of assisted reproduction and analysed retrospectively. On the basis of LH concentrations on stimulation day 7/8, the patients were divided into two groups: LH<1.2 IU/l (n=179) and LH>or=1.2 IU/l (n=522). Cycle outcomes were also compared on the basis of a ratio of mid- to early-follicular LH concentrations (0.5, n=491). RESULTS: Patients with low LH concentrations were found to have a significant reduction in the late-follicular estradiol concentrations (P<0.001), the number of oocytes retrieved (P<0.01) and the number of usable embryos (P<0.01), and they required significantly more rFSH (430 IU difference, P<0.01). These differences did not translate into a significant change in live birth rates. Conversely, a ratio of or=50%) was associated with a significant reduction in live birth rates per embryo transfer and per cycle started (27.3 versus 19.0%, P<0.05 and 22.2 versus 15.8%, P<0.05, respectively). CONCLUSIONS: Low mid-follicular levels of LH have a significant impact on ovarian response but not on live birth rates. A fall in LH level of >or=50% from the early- to mid-follicular phase resulted in a lower live birth rate.     

Ultrasound-guided soft catheter embryo transfers will improve pregnancy rates in in-vitro fertilization

Attempts to improve clinical pregnancy rates after in-vitro fertilization (IVF) and embryo transfer are constantly being made. Two changes in technique of embryo transfer of potential clinical importance were evaluated over two contiguous time periods in order to observe any corresponding change in clinical pregnancy (CP) rate per transfer: (i) embryo transfer catheter; (ii) ultrasound guidance. Catheter choices were hard: Tefcat, Tom Cat, or Norfolk; or soft: Frydman or Wallace. Ultrasound visualization was considered to be excellent/good when the catheter could be followed from the cervix to the fundus by transabdominal ultrasound with retention of the embryo-containing fluid droplet; fair/poor if visualization could not document the sequence of events. Embryo transfers were performed in 518 cycles. CP rates per transfer using soft and hard catheters was 36 and 17% (P < 0.000) respectively. CP rates per transfer for transfers performed with and without ultrasound guidance were 38 and 25% (P < 0.002) respectively. A statistically significant difference was also noted when visualization ranks were compared. CP rates per transfer in all excellent/good ultrasound-guided transfers was 41.5 versus 16.7% for fair/poor transfers (P < 0.038). In conclusion, performance of embryo transfer with a soft catheter under ultrasound guidance with good visualization resulted in a significant increase in clinical pregnancy rates.     

Characterization of a top quality embryo, a step towards single-embryo transfer.

In most in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programmes approximately one ongoing pregnancy in three is multiple. The need to characterize embryos with optimal implantation potential is obvious. We retrospectively examined all of 23 double transfers resulting in ongoing twins, occurring between January 1, 1996 and May 19, 1997. Characteristics of these top quality embryos were absence of multinucleated blastomeres, four or five blastomeres on day 2, seven or more cells on day 3, and 2 embryos, 11/31 (35%) were multiple. We applied our top quality criteria to the 221 double transfers: 106 transfers with two top embryos resulted in 65 (63%) ongoing pregnancies with 37 (57%) twins, 65 transfers with one top embryo in 38 (58%) ongoing pregnancies with eight (21%) twins. In the group without top embryos, 12/52 (23%) ongoing singletons occurred, with no twins. The corresponding ongoing implantation rates were 49, 35 and 12%. This analysis suggests that single embryo transfer with an acceptable pregnancy rate might be considered if a top quality embryo is available.     

Cost-effectiveness analysis of in-vitro fertilization: estimated costs per successful pregnancy after transfer of one or two embryos

Standard protocols for in-vitro fertilization (IVF) include transfer of two or three embryos. Not surprisingly, the rate of twin pregnancy after IVF is high (about 24% of all pregnancies). Routine transfer of one, rather than two, embryos would be expected to result in a much lower rate of twin pregnancies at the cost of a lower take-home baby rate. The aim of this study was to compare hypothetical costs to society incurred by pregnancies achieved with IVF protocols based on the transfer of one or two embryos. We compared actual (for two-embryo transfers) and hypothetical (for one-embryo transfers) take-home baby rates; risks of twin pregnancies; and costs of sick leave and hospitalization during pregnancy, deliveries, neonatal intensive care, and handicap care after transfer of one or two embryos. The study showed that even when more treatments might be needed to achieve similar baby take-home rates after transfer of one compared with two embryos, the lower twin pregnancy rate of the former approach caused it to be more cost-efficient than the latter. In conclusion, IVF costs are the sum of fertilization treatment costs and the costs for health care of the pregnant women and their offspring. Considering the association of the latter costs with numbers of embryos transferred, studies of one- embryo transfer protocols are urgently needed.