Take-home Baby Rate Research Articles

Clinical outcome of day 2 versus day 5 transfer in cycles with one or two developed embryos

Objective: To determine whether extended culture of embryos to blastocysts has any benefit in cycles with only one or two created embryos. Design: Retrospective analysis of cycles comparing outcomes of day 2 and day 5 transfers. Our day 2 group was from the year 1999 and our day 5 group, from the year 2000. Setting: Assisted reproductive technology program of a teaching hospital. Patient(s): All patients, irrespective of age, who had developed one or two embryos. Intervention(s): Stimulated IVF, intracytoplasmic sperm injection, or testicular sperm extraction and intracytoplasmic sperm injection cycles with 2-day culture in universal IVF medium (n = 133) or 5-day culture in BlastAssist media (MediCult, Jyllinge, Denmark; n = 132). Main Outcome Measure(s): Pregnancy, implantation, and take-home baby rates. Result(s): In the groups of 2-day and 5-day culture, embryo transfer was performed in 98% and in 57% of cycles, respectively. However, the total implantation rate per created embryo (18% vs. 18%), the pregnancy rate per cycle (23% vs. 21%), and the take-home baby rate (69.4% vs. 71.4%) did not differ between the day 2 and day 5 groups. Conclusion(s): Extended culture of embryos does not improve or decrease their capacity for implantation but only allows for better selection and is therefore not necessary in cycles with fewer than three embryos.

Impact of parental gonosomal mosaicism detected in peripheral blood on preimplantation embryos

This study evaluated the chromosomal condition of embryos generated by patients with an altered karyotype due to gonosomal mosaicism and the clinical outcome after preimplantation genetic diagnosis (PGD) for aneuploidy. Thirty-six patients aged 34.6 ± 3.6 years performed 54 treatment cycles and had 295 embryos diagnosed by fluorescence in-situ hybridization (FISH). Thirty-seven per cent of the embryos were chromosomally normal and generated 19 clinical pregnancies after replacement in 39 cycles. Only one pregnancy miscarried, yielding a take-home baby rate of 33.3%. Autosomal monosomy and trisomy contributed 36.1% of total abnormalities and gonosomal aneuploidy 5.9%, similar to the results detected in patients who undergo PGD for increased maternal age. Reanalysis was performed on 114 non-transferrable embryos: 41 were found to be mosaics, which were grouped in three different types, chaotic mosaics (56%), aneuploid mosaics (29%) and diploid/haploid/polyploid mosaics (15%). The incidence of aneuploid mosaics was higher than expected compared with PGD patients of the same age and resembled the condition observed in patients of advanced maternal age. These findings suggest that constitutional carriers of sex chromosome mosaicism are predisposed to autosomal mosaicism of embryos, possibly due to errors of cell division. There is an indication that this tendency is higher in female than male carriers.

Comparison of two blastocyst culture systems: coculture on Vero cells and sequential media

Objective: To compare two blastocyst culture systems: culture on Vero cells and sequential media in the same time period. Design: Retrospective study. Setting: Institutional practice assisted reproductive technology center. Patient(s): Ninety-nine selected patients undergoing IVF with blastocyst culture. Intervention(s): In vitro fertilization and transfer of at least one expanded blastocyst after culture using either Vero cells or sequential media (S 2 medium). Main Outcome Measure(s): Blastocyst, pregnancy, and implantation rates. Result(s): The blastocyst formation rate (41.6% vs. 31.6%) is significantly increased with sequential media compared with the coculture system, but there is no statistically significant difference in the pregnancy and implantation rates (39.5% vs. 38.6% and 23.7% vs. 15.1%, respectively). Conclusion(s): Blastocyst culture on sequential media offers a better dynamic of embryo development (22% vs. 13.6% blastocyst at day 5). There was no statistically significant difference between the two groups in the take-home baby rate (18 vs. 12).

Upper limit of the number of IVF-ET treatment cycles in different age groups, predicted by cumulative take-home baby rate

Upper limit of the number of IVF-ET treatment cycles in different age groups, predicted by cumulative take-home baby rate

Upper limit of the number of IVF-ET treatment cycles in different age groups, predicted by cumulative take-home baby rate.

Upper limit of the number of IVF-ET treatment cycles in different age groups, predicted by cumulative take-home baby rate.

Die Wirksamkeit des Komplexmittels Phyto-Hypophyson® L bei weiblicher, hormonell bedingter Sterilität. Eine randomisierte, placebokontrollierte, klinische Doppelblindstudie

Phyto-Hypophyson^(r) L for Female Infertility. Randomized, Placebo-Controlled, Clinical Double-Blind Study Objective and Design:In a prospective, randomized, placebo-controlled, double-blind study, the effects of Phyto Hypophyson L (Steierl-Pharma GmbH, Herrsching, Germany), an Agnus castus-containing homeopathic preparation, were investigated in 67 women with fertility disorders. Patients and Methods:37 women with oligomenorrhea and 30 women with amenorrhea received 50 drops of Phyto Hypophyson L or placebo 3 times a day over 3 months or 3 cycles. Outcome Measure and Results:The outcome measure being spontaneous menstruation, improved concentration of progesterone in the luteal phase, shortening of the cycle, earlier ovulation, and pregnancy was achieved in 38 out of 67 women. It was achieved more often from women with oligomenorrhea in the Phyto Hypophyson L group compared to the placebo group (82 versus 45%, p = 0.021). However, there was no significant effect when viewing the whole group. The baby take-home rate during the therapy and 6 months after the end of the therapy showed a ratio of 6 : 2 (18.7 : 6.4%). This result was not significant. Furthermore, in the oligomenorrhea verum group we observed a significant increase of progesterone during the luteal phase compared to the oligomenorrhea placebo group. Only very few undesirable drug effects were observed. Conclusion: In women with sterility and oligomenorrhea, a treatment with Phyto Hypophyson L can be recommended over a period of 3–6 months.

Fifteen years experience with an in-vitro fertilization surrogate gestational pregnancy programme.

The purpose of our study was to review and evaluate retrospectively the experience of an in-vitro fertilization (IVF) surrogate gestational programme in a tertiary care and academic centre. In a 15 year period from 1984 to 1999, a total of 180 cycles of IVF surrogate gestational pregnancy was started in 112 couples. On average, the women were 34.4 +/- 4.4 years of age, had 11.1 +/- 0.72 oocytes obtained per retrieval, 7.1 +/- 0.5 oocytes fertilized and 5. 8 +/- 0.4 embryos subsequently cleaved. Sixteen cycles (8.9%) were cancelled due to poor stimulation. Except for six cycles (3.3%) where there were no embryos available, an average of 3.2 +/- 0.1 embryos was transferred to each individual recipient. The overall pregnancy rate per cycle after IVF surrogacy was 24% (38 of 158), with a clinical pregnancy rate of 19% (30 of 158), and a live birth rate of 15.8% (25 of 158). When compared to patients who underwent a hysterectomy, individuals with congenital absence of the uterus had significantly more oocytes retrieved (P < 0.006), fertilized, cleaved and more embryos available for transfer despite being of comparable age. IVF surrogate gestation is an established, yet still controversial, approach to the care of infertile couples. Take-home baby rates are comparable to conventional IVF over the same 15 year span in our programme. Patients with congenital absence of the uterus responded to ovulation induction better than patients who underwent a hysterectomy, perhaps due in part to ovarian compromise from previous surgical procedures.

Pregnancy outcome in women with insulin-dependent diabetes mellitus complicated by nephropathy.

We retrospectively analysed pregnancy complicated by diabetic nephropathy in patients attending a University teaching hospital (1990-97), to examine fetal/maternal outcomes. Fetal outcomes included early intrauterine deaths, stillbirths, neonatal/perinatal mortality, size for gestational age, malformations, and need for neonatal unit care. Maternal outcomes included change in frequency of hypertension or severe proteinuria, serum creatinine data, and caesarean section rate. There were 21 pregnancies in 18 women, resulting in 21 live infants. Neonatal mortality (RR 10, 95% CI 0-3.9), perinatal mortality (RR 5, 95% CI 0-3.3) and congenital malformations (RR 5.0, 95% CI 0.3-26.3) were greater than in the background population. At delivery, 76% of babies were appropriate in size for gestational age; 57% were preterm, all of whom required neonatal unit care. The caesarean section rate was 90.5% vs. 20% in the background population (RR 4.5, 95% CI 3.4-5.0) (p < 0.05). Hypertension frequency (p < 0.001) and high-grade proteinuria (p < 0.05) increased from booking to delivery. Although the take-home baby rate was 90%, perinatal/neonatal mortality, congenital malformations and caesarean sections, in addition to maternal morbidity, were significantly higher in women with diabetic nephropathy than in the background population.

Selective Feticide in Twin Pregnancies with Very Early Preterm Premature Rupture of Membranes

Nine consecutive multichorionic multiple gestations with early second-trimester (< or =20 weeks) preterm premature rupture of the membranes (PPROM) of the lower gestational sac were managed expectantly. Mean gestational age at PPROM was 17.5 weeks (13-20 weeks), and the mean PPROM delivery time interval was 6.2 weeks (0-11 weeks). A fetal loss of 63% (12 of 19), and a subsequent neonatal loss of 57% (4 of 7) were observed. Of the four pregnancies evolving beyond 25 weeks, three delivered before 30 weeks. The baby take-home rate was 16% (3 of 19). Histologic evidence of chorioamnionitis was present in 5 of 7 (71%) investigated pregnancies. Three other consecutive twin pregnancies were complicated by PPROM of the precervical gestational sac at 13 to 16 weeks of gestation (mean: 15 weeks). In the absence of clinical chorioamnionitis and amniotic fluid, selective feticide with potassium chloride was performed. Pregnancy was successfully prolonged beyond 33 weeks in two cases. The overall PPROM delivery time interval was 21 weeks (20-22 weeks). No neonatal losses were encountered. The baby take-home rate was 66% (2 of 3). Selective feticide of the fetus with early midtrimester PROM in the absence of maternal signs of infection may improve the former unfavorable pregnancy outcome.

In vitro fertilization in women over 40 years of age. A study on retrospective data for eight years

A retrospective (1987–1995), single-center study was conducted to evaluate the IVF success rate in women who were 40 years and over. Controls were randomly selected patients who were 35 years or younger from the same center. The main evaluation criterion was the number of pregnancies initiated in each group and especially the number of full-term deliveries (take-home baby rate). Differences were considered as statistically significant for P≤0.05. A total of 194 IVF attempts in women 40 years or over were compared to 209 attempts in the control group. The mean ages of the two groups was 40.9 vs. 29.3 years (P<0.001). The duration of follicle stimulation was 12.9 vs. 13.1 days (not significant, NS). The number of ampules was 29.6 vs. 29.2 (NS). Serum estradiol levels were 1435.8 vs. 2020.8 pg/ml (P<0.001). Oocytes: 4.6 vs. 7.3 (P<0.001). Embryos: 1.7 vs. 2.8 (P<0.0001). Full-term deliveries: 3.6 vs. 13.4% (P<0.05). Better oocyte retrieval was achieved (5.3 vs. 3.3; P=0.001) in the group that was 40 years or over, but there were no differences in the rate of embryo transfer (1.9 vs. 1.3; NS) and full-term deliveries (4.2 vs. 2.9%) in a long protocol compared to a short one. The results of the study are similar to those found in the literature. Indications for standard IVF without oocyte donation should be carefully thought out and couples should be warned of the low success rate.

Treatment of Male Infertility Due to Sperm Surface Antibodies: IUI or IVF?

This prospectively designed study was aimed at comparing the results of two different treatment protocols in 29 infertile couples with proven male immunological infertility, i.e. a positive (>50%) mixed antiglobulin reaction (MAR) test (IgG and/or IgA). In the first protocol (group I, n = 14) couples were treated with ovarian stimulation/ intrauterine insemination (IUI), followed by in-vitro fertilization (IVF) if no pregnancy occurred after three IUI cycles. In the second protocol (group II, n = 15), patients were treated with IVF as a first choice procedure. The decision to follow protocol 1 or 2 was made by the couples after information about financial costs and expected success rates (according to the literature) for both treatment options. In group I, nine patients (64.3%) conceived after a maximum of three IUI cycles whereas seven patients (46.6%) of group II became pregnant during the first IVF cycle. The take-home baby rate per started IUI or IVF cycle was 27.3% (9/33) and 44.4% (16/36) respectively with a take-home baby rate of 64.3% after three IUI cycles and 93.3% after three IVF attempts. To conclude, both IUI and IVF yielded unexpectedly high pregnancy rates in this selected group of patients with long-standing infertility due to sperm surface (predominantly IgG) antibodies. Since cost benefit analysis comparing superovulation IUI with IVF may favour a course of four IUI cycles, we advocate superovulation IUI as the first line therapy in male immunological infertility.

Intrauterine insemination after ovarian stimulation with clomiphene citrate: predictive potential of inseminating motile count and sperm morphology.

This retrospective study aimed to evaluate the prognostic value of the inseminating motile count (IMC) and sperm morphology (using strict criteria) on success rates after homologous intrauterine insemination (IUI) combined with clomiphene citrate (CC) stimulation. A total of 373 couples underwent 792 IUI cycles in a predominantly (87.4%) male subfertility group. The overall cycle fecundity (CF) and baby take-home rate (BTH) was 14.6 and 9.9% respectively. The cumulative CF and BTH (per couple) after three cycles were 30.6 and 21.1% respectively. Overall, sperm morphology and IMC were of no prognostic value using receiver operating characteristic (ROC) curve analysis, but after classifying the study population into different subgroups according to IMC, sperm morphology turned out to be a valuable prognostic parameter in subgroup 1, i.e. IMC <1 x 10(6). In this subgroup, no pregnancies were seen when the morphology score was <4% and the mean value of sperm morphology was significantly different in the pregnant (8.3%) versus non-pregnant group (5.0%; P <0.05). The cumulative CF and BTH after three IUI cycles were comparable for all couples with the exception of those cases in which the IMC was <1 x 10(6) with a morphology score of <4% normal forms. We recorded only two twin pregnancies (2.5%) and no moderate or severe ovarian hyperstimulation syndrome. We conclude that in a selected group of patients without CC resistance and normal ovarian response following CC stimulation [maximum of three follicles with a diameter of >16 mm at the time of administration of human chorionic gonadotrophin (HCG)], IUI combined with CC-HCG can be offered as a very safe and non-expensive first-line treatment, at least with an IMC of >1 x 10(6) spermatozoa. In cases with <1 x 10(6) spermatozoa, CC-IUI remains important as a first-choice therapy provided the morphology score is > or =4%.

Single versus double insemination: a retrospective audit of pregnancy rates with two treatment protocols in donor insemination.

Our objective was to evaluate the effect of a change in treatment protocols, suggested following an inspection visit by the regulatory authority, from single to double inseminations during donor insemination treatment cycles. We therefore conducted a retrospective audit of pregnancy rates in the reproductive medicine clinic of a major teaching hospital. All patients were treated for male factor infertility by donor insemination, without ovulation induction with gonadotrophins between October 1992 and December 1995. The main outcome measures were cumulative conception and live birth rates. During the study period 250 patients underwent treatment and 650 single insemination and 277 double insemination treatment cycles were undertaken. The pregnancy rate per cycle was 0.054 and 0.119 for single and double insemination respectively. After six cycles the cumulative pregnancy rates were 0.28 and 0.47 and the take-home baby rates were 0.25 and 0.37 for single and double inseminations respectively. The change in practice from single to double insemination resulted in a doubling of the pregnancy rate per treatment cycle. Cumulative pregnancy rates after two treatment cycles of double insemination were comparable with those achieved after six cycles of single insemination. These results have significant implications for both patients and purchasers.

Assisted hatching by zona drilling of human embryos in women of advanced age

The study was conducted to examine the efficacy of the zona drilling technique for promotion of successful implantation and pregnancy by assisting embryo hatching in women of advanced age undergoing treatment by in-vitro fertilization. A total of 839 embryos from 211 patients aged >38 years underwent assisted hatching during 312 cycles of therapy. The outcome of this micromanipulation procedure was compared to 540 non-hatched pre-embryos transferred to 174 patients during 274 cycles of therapy. Assisted hatching was performed on four- to eight-cell stage embryos using the zona drilling technique. In the assisted hatching group, 839 micromanipulated embryos were replaced (two to four embryos per patient) compared to 540 embryos transferred in the control group. Despite the fact that the pregnancy rate was not statistically different between the groups (8.9% in the assisted hatching group versus 5.1% in the controls) a trend towards an increase was noted in the assisted hatching group. The implantation rate was 3.75 and 3.55% per patient respectively, and there was no significant difference in abortion rate between the groups. The delivery rate was 3.8 and 3.4% per cycle respectively. The results of this study demonstrated that assisted hatching by zona drilling in a selected group of patients aged >38 years does not increase the take-home baby rate after in-vitro fertilization treatment.

High tubal damage grade is associated with low pregnancy rate in women undergoing in-vitro fertilization treatment.

In order to analyse the relationship between grade of tubal damage and pregnancy rate following in-vitro fertilization (IVF) treatment, 50 consecutive couples with isolated tubal infertility who underwent IVF without previous reconstructive surgery were studied. The couples had tried to conceive for 2.5-5.6 years (mean 3.9 years) and had gone through a complete investigation for infertility. All women fulfilled the standard criteria for normal ovulatory cycles. All males had normal spermiograms. Tubal function was in each case evaluated by hysterosalpingography and laparoscopy. Grade of tubal damage was classified on a scale of I-IV. Patients with milder tubal damage (groups I-II) showed considerably higher take-home baby rate per started cycle (48%) than patients with severe tubal damage (group IV; 6%) (P < 0.001) even though patients in group IV underwent more treatment cycles than patients in groups I-II (2.7 versus 1.8; P < 0.01). In the first treatment cycle nine out of 12 patients in groups I-II became pregnant as compared with only one out of 16 in group IV (P < 0.01). As indicators of lower ovarian response, the women in group IV needed a higher number of gonadotrophin ampoules per cycle (P < 0.001) and exhibited lower pre-ovum retrieval oestradiol concentrations (P < 0.001). Oocyte retrievals per started cycle (I-II: 100%; III: 98%; IV: 84%) did not differ significantly between the groups, neither did pre-embryo replacements (I-II: 95%; III: 80%; IV: 73%) nor pre-embryos per replacement (I-II: 3.0; III: 2.9; IV: 2.8). The present results concerning the role of tubal damage grade for the outcome of IVF treatment should be considered in patient counselling. Further studies are needed to elucidate the mechanisms by which the extent of tubal damage may impair ovarian function and reduce IVF outcome.

Reproductive health care policies around the world. ART practice in Singapore.

ART practice in Singapore is monitored by the MOH, with guidance from an Advisory Committee on HRE. All centers and practitioners must be licensed. Data collection is by means of three forms. Based on the submissions, the averages for all centers in Singapore for the 5 years 1990 to 1995 were as follows: clinical pregnancies averaged 16.4% per cycle and 22.6% per replacement, and take-home baby rates averaged 11.5% per cycle and 15.9% per replacement.

Intracytoplasmic sperm injection — ICSI

For more than a decadein vitrofertilization (IVF) has been successful in the treatment of couples with long-standing infertility due to various aetiologies such as tubal disease, male-factor infertility, unexplained infertility and endometriosis. The usual fertilization rate in IVF for nonmale infertility cases is 60–70% of the inseminated cumulus-oocyte complexes and in andrological infertility it is only 20–30%. The lower the number of normally fertilized oocytes, the less chance there is of available embryos, so that patients may have no embryos to transfer. It has been the experience of all centres for reproductive medicine, including our own, that a certain number of couples with male-factor infertility cannot be helped by standard IVF treatment. After insemination with progressively motile spermatozoa the number of two-pronuclear oocytes was either zero or less than 5%. Furthermore, a sizeable number of couples cannot be accepted for IVF if the number of progressively motile spermatozoa in the ejaculate is below a certain threshold number such as 500 000. In the past five years, assisted fertilization procedures have been developed to circumvent the barriers that prevent sperm access to the ooplasma, namely the zona pellucida and the ooplasmic membrane. Pregnancies and births have been reported after partial zona dissection (PZD) and subzonal insemination (SUZI). The success rate of PZD and SUZI has remained moderate: the normal fertilization rate (two-pronuclear oocytes) has never exceeded 20–25% of the micromanipulated oocytes; only two-thirds of the patients have had embryo transfers of, usually, a low number of embryos, resulting in a reduced pregnancy and take-home baby rate.

Should gonadotropin-releasing hormone down-regulation therapy be routine in in vitro fertilization?

To compare the classic clomiphene citrate (CC) and hMG regime for ovarian stimulation before IVF in women who received hMG post-long protocol down-regulation with either 3 mg triptorelin [INN] IM or 150 mg buserelin acetate four times daily intranasally. Furthermore, if possible, to determine the preferred method of down-regulation. A prospective study of 150 women randomized blind to the clinician to one of three alternative ovarian stimulation regimes when passing for the first time through an IVF program during 1992. Triptorelin [INN] down-regulated significantly more quickly than buserelin acetate. The non-down-regulated group CC and hMG used significantly less hMG in a shorter time. In these women LH levels at hCG administration were significantly higher. No other intergroup differences were found. Pregnancy and take-home baby rates for the overall study were, respectively, 32%:25% (per cycle) and 42%:33%; (per ET) for the triptorelin [INN] group 28%:22% and 39%:31%; the CC group 32%:24% and 46%:34%; and the buserelin acetate group 34%:28% and 42%:34%. Triptorelin [INN] and buserelin acetate were comparable in all parameters except down-regulation. The former was significantly quicker and more sure. In none of the clinical end points measured, however, was the classic CC and hMG non-down-regulation regime significantly less effective or troublesome than where down-regulation was used. These results therefore show that although indications for down-regulation before IVF exist, it should not be used on all patients.

Simplification of IVF: minimal monitoring and the use of subcutaneous highly purified FSH administration for ovulation induction

During the past few years much effort has been put into simplifying the clinical management of in-vitro fertilization/embryo transfer cycles. One important step was the introduction of transvaginal ultrasound-guided oocyte collection, as previously described. This study describes further simplifications of the clinical management of ovarian stimulation. During the period 1st January 1991 to 31st August 1993, three major simplification steps were introduced. All cycles were down-regulated with a gonadotrophin-releasing hormone (GnRH) agonist according to a long protocol permitting fairly precise programming of the oocyte collection. During period I (n = 329 cycles), closer monitoring by several pelvic ultrasound scans and serum oestradiol was used for monitoring the ovarian stimulation. During period II (n = 230 cycles), only one ultrasound scan was used for monitoring the ovarian cycle; oocyte collections during weekends were avoided. During period III (n = 386 cycles), further simplification of the clinical management was introduced by using a highly purified follicle stimulating hormone (FSH) (Fertinorm/Metrodin HP), which was self-administered s.c. for ovarian stimulation. The take-home baby rates per started cycle for periods I, II and III were 16.4, 32.6 and 31.3% respectively. These figures indicate that when using long down-regulation with a GnRH agonist, simplification of the monitoring of the ovarian stimulation is possible without decreasing the pregnancy rate. Furthermore, the use of a highly purified FSH, self-administered s.c., greatly simplified treatment without compromising cycle outcome or increasing the risk of developing an ovarian hyperstimulation syndrome.

Subzonal insemination (SUZI) or in vitro fertilization (IVF) in microdroplets for the treatment of male-factor infertility

The results of subzonal insemination (SUZI) and in vitro fertilization with microdroplet insemination used in couples with male-factor infertility are presented. The total fertilization rate was 17.4% for SUZI (n = 89) and 49.3% for microdroplet IVF (n = 100). The fertilization rate for standard IVF (n = 510), not including any male-factor infertility and performed during the same period, was 73.2%. The "take-home baby rate" per started cycle and per embryo transfer (ET), respectively, was 10 and 17.6% for SUZI and 20 and 24.7% for microdrop IVF. For standard IVF these figures were 27 and 31.7%. It was concluded that microdroplet IVF can be used with good results in cases of moderate male-factor infertility. The normal (2PN) fertilization rate with the SUZI technique was only 15.1%. However, despite the low fertilization rate, SUZI should be considered when dealing with severe male-factor infertility.