Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilization-embryo transfer

Although it has been claimed that allografts of blood vessels might be successful because of minimal immunogenicity, they are subject to frequent and early failure, the cause of which has not been thoroughly investigated. We sought to define the immune response to allograft bypass. In a prospective trial, 40 patients underwent cryopreserved venous allograft bypass. Allograft biopsies were performed at implantation and at allograft explantation in instances of graft failure. Tissues were evaluated in a blinded manner by means of standard histologic examination and paraffin immunohistochemical analysis with monoclonal antibodies against a variety of immune markers. During the 31-month follow-up period, 22 allografts were removed, and 19 were suitable for immunohistochemical study. Of these 19, 6 (32%) had moderate or severe infiltrates, which were evenly distributed throughout the intima, media, and adventitia. Immunohistochemical study of the explants demonstrated all of these infiltrates to be leukocytes (+LCA), which were predominantly activated T lymphocytes (+CD3, CD8, CR3) containing cytotoxic granules (+TIA-1). Macrophages were uncommon (+CD68); B cells (+L26, CD79) and natural killer cells (+CD56) were rare. Immunosuppression was associated with decreased presence of cytotoxic granules (TIA-1). Human venous allografts are immunogenic and prompt a T cell-mediated response. Allografts also fail without strong evidence of rejection, presumably because of local injury, hypercoagulability, or stasis. It may be possible to modify the contribution of rejection to venous allograft failure by means of immunosuppression and to modify the contribution of local hypercoagulability by means of anticoagulation.     

Natural cycle in vitro fertilization-embryo transfer at the University of Ottawa: an inefficient therapy for tubal infertility

OBJECTIVE: To describe our experience with natural cycle IVF making clinical and endocrine comparisons with our standard stimulated cycle IVF program. DESIGN: We attempted 75 natural IVF-ET cycles with hCG given to preempt the LH surge and compared these with 450 attempts at standard superovulation IVF-ET done in our unit during the same time period. PATIENTS: Natural cycle patients are normally ovulating women < age 38. Superovulation IVF-ET patients are all < 41 years old. Patients in both groups had partners with normal semen parameters and tubal factor infertility. MAIN OUTCOME MEASURES: Cancellation rates, pregnancy rates per egg retrieval, per ET procedure, and luteal phase E2:P ratios of the treatment cycles are compared. RESULTS: There were 35 of 75 (47%) natural cycle and 112 of 450 (25%) superovulation cycle cancellations. An egg was retrieved in only 24 of 40 (60%) natural cycles and 336 of 338 (99%) superovulation egg retrieval procedures. Pregnancy rates per ovum pick-up procedure were significantly higher: 65 of 338 (19%) in the superovulation versus 2 of 40 (5%) in the natural cycle groups. Pregnancy rates per ET were not significantly different between natural IVF-ET, 2 of 18 (11%) and superovulation IVF-ET, 65 of 298 (22%). The E2:P ratios 5 days after ET were similar in both groups at 18 +/- 4 after natural IVF-ET and 21 +/- 18 after superovulation IVF-ET. CONCLUSIONS: [1] Cancellation rates for natural cycle IVF are very high. [2] Midluteal E2:P ratios are the same in both groups. [3] Pregnancy rates per egg retrieval are significantly lower for natural versus superovulation IVF-ET. [4] In our experience, natural cycle IVF-ET is an inefficient therapy for tubal infertility compared with superovulation IVF-ET.     

An android body fat distribution in females impairs the pregnancy rate of in-vitro fertilization-embryo transfer

To assess if the waist:hip ratio (WHR) is associated with the pregnancy rate (PR) in in-vitro fertilization (IVF) and embryo transfer, waist and hip girths, in addition to height, weight, body mass index (BMI), indications for IVF, PR and other related variables, were measured in 220 women undergoing IVF-embryo transfer. Three variables were significantly negatively associated with PR; high age, smoking and WHR >0.80. Women with WHR between 0.70-0.79 had a PR of 29.9% as compared to 15.9% in women with WHR >0.80 [odds ratio 0.42, 95% confidence interval (CI) 0.2-0.9, P = 0.03]. There were no correlations between BMI and PR, nor were there any significant differences for the indications for IVF-embryo transfer, number of oocytes or oocyte fertilization rate, cleavage rate and number of embryos transferred. The association between a low PR and WHR >0.80 remained unchanged after adjustment for age, BMI, smoking, indication for IVF, parity and number of embryos transferred. In IVF-embryo transfer, fertilization is a laboratory and clinically controlled process, until the embryo is transferred to the uterus. Possible reasons for our finding of a decreased PR in women with an android body fat distribution include a different endocrinological and biochemical milieu for the oocyte in the growing follicle, oocytes of poor quality, or endometrial changes due to hormonal dysfunction.     

Influence of antithyroid antibodies in euthyroid women on in vitro fertilization-embryo transfer outcome

The direct synthesis and subsequent rapid characterisation of multiple antigen peptides (MAPs) for use as immunogens has presented difficulties, partly because of the formation of incomplete or truncated peptide sequences during the synthetic procedure. Therefore, many researchers have resorted to ligation procedures for the synthesis of MAP constructs. This article describes a method to improve the yield of MAP constructs by direct synthesis methods, as well as a general procedure that enables easier characterisation of the synthetic products. In particular, during the synthesis of MAP constructs, a capping procedure was introduced after each amino acid coupling step, thus improving significantly the yield of the desired multi-dendritic peptidic immunogens. Through the use of this capping procedure, problems arising from the incomplete amino acid residue coupling at the point of synthesis were minimised, and any deletion peptides which formed could be eliminated more readily during the subsequent purification procedures. In addition, previous difficulties in purification and characterisation of MAP construct by, e.g. electrospray mass spectroscopy (ES-MS), often led to the multi-dendritic peptidic immunogens being used without full characterisation after dialysis and recovery of the product(s). This article describes an enzymatic (tryptic) digestion method with the MAP construct, followed by characterisation of the enzymatic digest by reversed phase high-performance liquid chromatography-ES-MS. With this method, fragments of the MAP construct cleaved at specific amino acid residue sites (e.g. lysine or arginine) within the sequence of the parent peptide can be readily determined and the kinetics of the digestion easily followed. This enzymatic digestion procedure thus provides a facile approach to confirm that all of the multi-dendritic arms of the purified MAP construct have been equivalently elongated during the peptide synthesis and that consequently the purified construct structure contains the correct peptide sequence.     

Use of recombinant human follicle-stimulating hormone for in vitro fertilization-embryo transfer after severe systemic immunoglobulin E-mediated reaction to urofollitropin

OBJECTIVE: To report the successful use of recombinant human FSH in a patient with a history of a severe systemic immunoglobulin E (IgE)-mediated reaction to urofollitropin. SETTING: University hospital. PATIENT: A 38-year-old infertility patient who had experienced a whole-body rash with hives, tachycardia, fever, and other symptoms after urofollitropin administration, with confirmation of IgE-mediated sensitivity to urofollitropin by intradermal skin testing. INTERVENTION: In vitro fertilization-ET after the use of recombinant human FSH to stimulate ovarian follicular development. RESULTS: Establishment of a clinical pregnancy. CONCLUSIONS: Our case provides evidence for the involvement of nongonadotropin proteins as the direct cause of some adverse reactions from conventional urine-derived human FSH preparations.     

In vitro fertilization/embryo transfer in unexplained infertility and minimal peritoneal endometriosis

BACKGROUND: To compare the outcome of in vitro fertilization/embryo transfer (IVF-ET) in unexplained infertility and infertility associated with minimal peritoneal endometriosis. METHODS: A retrospective analysis comparing results of stimulation, sperm characteristics, cleavage, implantation and pregnancy rates in patients with unexplained infertility and peritoneal endometriosis associated infertility. Couples with tubal infertility constituted a control group. RESULTS: In the unexplained infertility and endometriosis groups similar response to stimulation, similar sperm characteristics and cleavage rates were observed. Compared with tubal infertility lower sperm motility was seen in the unexplained infertility group. Both non tubal infertility groups had lower cleavage rate than was seen in the control group. No differences in pregnancy rate were observed, but a significantly higher implantation rate was seen in unexplained infertility compared with tubal infertility. CONCLUSIONS: Couples with unexplained infertility and infertility associated with minimal peritoneal endometriosis have similar outcomes in an IVF-ET set up. Significantly lower cleavage rates in these groups compared with tubal infertility indicate gamete defects as possible causes of infertility.     

Children conceived by in vitro fertilisation after fresh embryo transfer

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.     

Ongoing normal pregnancy after transfer of zona-free blastocysts: implications for embryo transfer in the human

Recent reports suggest that transfer of day 5 blastocysts improves implantation rates in in-vitro fertilization programmes. This paper reports a successful ongoing pregnancy after the transfer of zona-free day 6 expanded and hatching blastocysts. The patient was 37 years old and had undergone six stimulated and two thaw cycles previously, all of which had failed. Stimulation was by down-regulation and oocytes recovered transvaginally by ultrasound guidance. Two pronuclear embryos were co-cultured on Vero cells to day 6. The zonae of two hatching and two fully expanded blastocysts were removed using 0.5% pronase, and the zona-free blastocysts were then transferred. Pregnancy was confirmed on day 18 with a positive human chorionic gonadotrophin (HCG) and ultrasound at 6 weeks showed a single healthy fetal heart inside a clear sac. At 14 weeks a triple test (oestriol, J-HCG and alpha-fetoprotein) was normal and at 22 weeks a detailed ultrasound scan showed no congenital anomalies. This is the first report in the human of a normal ongoing pregnancy after the transfer of zona-free day 6 embryos.     

Hormone replacement for pregnancy in functionally agonadal women after transfer of thawed embryos in the in vitro fertilization program--problems of placental incompetence

Experience with hormonal substitution of sterile women treated within the IVF programme by means of donated oocytes changed completely views on endocrinological prerequisites of successful implantations and the further development of early pregnancy. While the effect of oestrogens and progesterone on endometrial proliferation and receptivity has been elaborated in great detail in the literature, data on the substitution of early pregnancy and the onset of placental competence are much scarcer. 1. The placenta is during the 15th week of pregnancy already fully competent and hormonal substitution can be probably terminated already sooner. 2. From the shape of the curves (as compared with steroid levels in spontaneous pregnancies) the authors conclude that the used doses (in particular of progesterone were higher than physiological. 3. Pregnancy of women with primary or secondary ovarian failure is an ideal in vivo model for investigation of the receptivity of the endometrium, the problem of implantation and function of the foetoplacental unit. Available data are not uniform and therefore in this very interesting field further investigations are needed.     

Ectopic pregnancy in the stump of the uterine tube after in vitro fertilization

A rare case of ectopic pregnancy in stump of uterine tube after IVF, which was done after bilateral removal of uterine tubes, caused by uterine tube pregnancies was described. Diagnostic difficulties were shown in that case.     

Cumulative pregnancy and live birth rates after gamete intra-Fallopian transfer

To evaluate the efficacy of gamete intra-Fallopian transfer (GIFT) the Kaplan-Meier life table method was used to analyse a patient cohort treated with GIFT between 1991 and 1994. In a tertiary referral centre for reproductive medicine, 1628 women with a median age of 33 years and various causes of infertility were included to calculate cumulative pregnancy and live birth rates. Age and cause of infertility were main factor variables and the study was based on a total of 2941 consecutive GIFT cycles, leading to a first clinical pregnancy, and 3052 cycles, leading to a first live birth. The cumulative pregnancy and live birth rates were 49.6 and 38.8% respectively, after three initiated cycles and 64.1 and 52.0% respectively, after five initiated cycles. The multiple pregnancy rate was 22.6%. The implantation rate of 13.1% after GIFT demonstrates that the developing embryo benefits from a period of exposure within the environment of the Fallopian tube. The present results indicate that approximately 50% of couples will have at least one live baby after five initiated GIFT cycles. Advancing age was a major negative prognostic factor for the cumulative live birth rate because of higher cancellation rates, lower implantation rates and higher pregnancy failure rates.     

Does previous salpingectomy improve implantation and pregnancy rates in patients with severe tubal factor infertility who are undergoing in vitro fertilization? A pilot prospective randomized study

Systemic sclerosis (SSc; scleroderma) results in the excessive deposition of extracellular matrix components in affected organs. This is partly due to enhanced synthesis; however, the role of degradative processes in this disease is still poorly understood. Sera of 32 patients with SSc (22 with the diffuse, 10 with the limited form) and of six patients with morphoea were assessed using radioimmunoassays for the cross-linked carboxy terminal telopeptide of type I collagen (ICTP) and for the amino terminal propeptide of type I procollagen (PINP) reflecting type I collagen degradation and synthesis, respectively. In 27 of the 32 patients with SSc, the concentration of ICTP was above the upper limit of the normal value (4.6 micrograms/L) and the mean level was clearly elevated at 7.92 micrograms/L. The ICTP concentration correlated with the skin score measuring the extent of the lesions, whereas no such correlation was found for PINP. The ICTP antigen in serum, studied by immunoblotting, had a molecular weight of about twice that of the trypsin-generated fragment isolated from human bone collagen. The mean concentration of serum PINP was 43.9 micrograms/L and no patient exceeded the upper limit of the normal range (80 micrograms/L). We report here for the first time that the concentration of the type I collagen degradation product ICTP in serum shows a close correlation with the extent of skin fibrosis in patients with SSc. We conclude that the increased deposition of type I collagen in this disease is accompanied by an increased turnover of this molecule, indicating a more complex derangement of synthetic and degradative processes than previously acknowledged.     

Severe ovarian hyperstimulation syndrome and tubal pregnancy after in vitro fertilization

We report a case of a 38 year old woman with tubal pregnancy and severe ovarian hyperstimulation syndrome (OHSS) following in-vitro fertilization and intrauterine embryo transfer. The diagnostic and therapeutic problems in the coexistence of ectopic pregnancy and OHSS are discussed both in terms of the case-history and the literature.     

Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer

OBJECTIVE: To determine if an increase in plasma P occurring before hCG administration might impair the outcome of IVF-ET. DESIGN: Five hundred eighty-five IVF-ET cycles were prospectively studied for the occurrence of plasma P elevation before hCG administration. SETTING: Tertiary institution, IVF-ET program, H?pital A. Béclère. PATIENTS: Participating patients included IVF-ET candidates 23 to 42 years of age only, excluding the couples in whom a male factor was a primary or an accessory cause of infertility. MAIN OUTCOME MEASURES: To clarify the practical consequences on IVF-ET outcome of pre-hCG increases in plasma P, we studied 585 consecutive IVF-ET cycles. These were divided into two groups according to plasma P levels observed on the day of hCG administration; plasma P of 0.9 ng/mL (2.9 nmol/L) was taken as an arbitrary cutoff value. Group A included 485 IVF cycles in which plasma P was < or = 0.9 ng/mL (2.9 nmol/L); group B included the remaining 100 cycles in which plasma P was > 0.9 ng/mL (2.9 nmol/L). RESULTS: The number of mature oocytes retrieved, the oocyte cleavage rate, and the number of embryos obtained were similar in groups A and B. In contrast to this apparent similarity in oocyte quality, a decrease in pregnancy rate (PR) and a trend for a decrease in embryo implantation rate were observed in group B in comparison with group A. CONCLUSIONS: The similar fertilization and cleavage rates obtained in groups A and B suggest that pre-hCG elevation in plasma P does not lead to decreased oocyte quality. Yet the lower PR observed when plasma P rises prematurely suggests that the prolonged but discrete elevation in plasma P occurring in these cases might alter endometrium receptivity to embryo implantation.     

Midtrimester maternal serum screening after multifetal pregnancy reduction in pregnancies conceived by in vitro fertilization

BACKGROUND: The rising incidence of esophageal adenocarcinoma in western countries requires a new strategy in the management of dysplasia in Barrett's esophagus. Esophagectomy, which has high morbidity and mortality rates, has been recommended to treat patients with severe dysplasia. Strictly superficial laser coagulation with tissue ablation therefore is a desirable option for the management of dysplasia in Barrett's esophagus because the tissue to be ablated is only about 2 mm thick. Potassium-titanyl-phosphate (KTP) laser light with a wavelength of 532 nm is preferentially absorbed by hemoglobin and therefore combines excellent coagulation with limited tissue penetration. We report first clinical results with KTP laser superficial vaporization of dysplasia and early cancer in Barrett's esophagus. METHODS: Eight men and 2 women 43 to 84 years of age with short segments of Barrett's esophagus or traditional Barrett's esophagus and histologically proved low-grade (n = 4) and high-grade (n = 4) dysplasia or early adenocarcinoma (n = 2) were selected for this pilot study. For all patients thermal endoscopic destruction was conducted with a frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG) KTP laser system. Laser therapy was performed by means of the free-beam method with coaxial insufflation of gas. An average of 2.4 sessions per patient were required for ablation of the Barrett's mucosa. RESULTS: Two to three days after laser treatment the response of the ablated mucosa was assessed with endoscopy and biopsy. Samples taken showed fibrinoid necrosis of the mucosal layer. A complete response was obtained for all 10 patients. Replacement by normal squamous cell epithelium was induced in combination with acid suppression therapy of up to 80 mg omeprazole daily. No complications occurred. In two patients biopsy showed specialized mucosa beneath the restored squamous cell epithelial layer. Follow-up times were as long as 15 months (mean value 10.6 months). CONCLUSIONS: KTP laser destruction of Barrett's esophagus induced mucosal regeneration with normal squamous cell epithelium in combination with acid suppression. Limitation of the depth of thermal destruction in Barrett's esophagus minimizes risk for perforation or stricture formation. KTP laser ablation of Barrett's esophagus seems to be feasible and safe in short segments of Barrett's esophagus with dysplasia or early cancer.     

Success rates with gamete intrafallopian transfer and in vitro fertilization in women of advanced maternal age

OBJECTIVE: To evaluate the effect of maternal age on outcomes for IVF and GIFT in women 40 to 45 years of age. DESIGN: Retrospective. SETTING: Boston IVF, a free-standing university-affiliated IVF and GIFT unit. PATIENTS: A total of 2,931 cycles of IVF and 1,826 cycles of GIFT were analyzed in women undergoing assisted reproductive technologies (IVF or GIFT) using autologous eggs. INTERVENTIONS: Medical records of patient outcomes were reviewed. RESULTS: For patients undergoing IVF, the cancellation rate for initiated cycles showed significant differences in women aged 25 to 39 (38.3%), women aged 40 to 43 (49.5%), and women aged 44 to 45 years (69.5%). A significantly lower delivery rate per stimulation and delivery rate per retrieval was found in women aged 40 to 43 years when compared with women aged 25 to 39 years. No deliveries occurred in 59 cycles in women aged 44 to 45 years, thereby representing a significant difference when compared with both women aged 25 to 39 years and women aged 40 to 43 years. For patients undergoing GIFT, the cancellation rate for initiated cycles was significantly higher in women aged 40 to 43 (25.0%) and 44 to 45 years (31.0%) when compared with women aged 25 to 39 years (15.1%). A significantly lower delivery rate per stimulation and delivery rate per retrieval was found in women aged 40 to 43 and 44 to 45 years when compared with women aged 25 to 39 years. CONCLUSIONS: Success rates for IVF and GIFT decline significantly in women > 40 years old. Women aged > or = 44 years are unlikely to benefit from the use of IVF and GIFT.