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Biomedical subjects

J A Land

Publications and source records attributed to J A Land.

At least 37 records · Page 2Linked to original sources

Treatment-independent pregnancy rate in patients with severe reproductive disorders.

A long waiting list for in-vitro fertilization (IVF) offers the possibility to study treatment-independent pregnancy rates in patients with severe reproductive disorders. We performed a retrospective cohort study with a nested case-control design in which the cases achieved a spontaneous pregnancy while on the waiting list for IVF, or for IVF with intracytoplasmic sperm injection (ICSI), and the controls did not become pregnant while on the waiting list. Spontaneous pregnancies occurred in 76 of 1391 patients on the waiting list. Significant differences between pregnant and non-pregnant patients were found for duration of subfertility (couples on the IVF waiting list), and for progressive sperm motility and basal 17beta-oestradiol (couples on the ICSI waiting list). The 12 months cumulative pregnancy rate for patients on the waiting list was 2.4% (95% CI 1.2-3.9%) for tubal subfertility patients, 5.9 % (3.7-8.7%) for longstanding unexplained subfertility patients, and 6.6% (4.5-9.3%) for male subfertility patients. Of the 76 control patients, 21% of tubal subfertility patients, 18% of unexplained subfertility patients, and 17% of male subfertility patients achieved a pregnancy in their first IVF or ICSI treatment cycle. We confirm that the treatment-independent pregnancy rate in patients with severe reproductive disorders is low. More than 75% of the spontaneous pregnancies in the tubal subfertility and unexplained subfertility couples occurred during their first three months on the waiting list, whereas spontaneous pregnancy rate in male subfertility couples showed a more gradual but persisting increase. We conclude that one cycle of IVF or ICSI is superior to 12 months of expectant management in patients with severely impaired fertility due to tubal, unexplained or male factors.

Adult↗

Patient dropout in an assisted reproductive technology program: implications for pregnancy rates.

OBJECTIVE: To study patient dropout and its impact on crude and cumulative pregnancy rates (PRs) after assisted reproductive technology (ART). DESIGN: Retrospective cohort study. SETTING: University hospital-based tertiary care fertility clinic. PATIENT(S): Two hundred two couples applying for their first ART treatment cycle. MAIN OUTCOME MEASURE(S): Drop-out rate and PR per cycle, cumulative drop-out rate and cumulative PR. RESULT(S): After three treatment cycles, the cumulative drop-out rate was 126 of 202 (62.4%); 13.9% (n = 28) was due to active censoring. Active censoring was shown to flatter cumulative PRs by life-table analysis. CONCLUSION: Dropout from ART is high, even when ART costs are covered by health cost insurance. Life-table analysis overestimates cumulative PRs in ART.

Cohort Studies↗

High-dose human menopausal gonadotropin stimulation in poor responders does not improve in vitro fertilization outcome.

OBJECTIVE: To study the outcome in poor responders to three ampules (225 IU) of hMG per day in subsequent IVF treatment cycles in which six ampules (450 IU)of hMG per day were administered. DESIGN: Retrospective chart review. SETTING: Academic tertiary center. PATIENTS: Between January 1988 and May 1995, 126 poor response patients had a first treatment cycle on three ampules and a second cycle on six ampules of hMG per day. MAIN OUTCOME MEASURES: Numbers of follicles, oocytes, and embryos, and pregnancy rates. RESULTS: On six ampules, patients had significantly more follicles and oocytes. The number of embryos did not differ significantly. The pregnancy rate on six ampules were low (3.2% pregnancies per cycle started). CONCLUSION: Poor responders do not benefit from high-dose hMG stimulation; their reproduction outcome is poor.

Adult↗

Constitution of semen samples from XYY and XXY males as analysed by in-situ hybridization.

A brightfield microscopical in-situ hybridization (ISH) technique was applied to semen samples of two 47,XYY males, one 46,XY/47,XXY/XXY male with fertility problems, and two normal 46,XY men, who served as controls. The use of a standardized nuclear DNA decondensation method, together with double-target ISH and morphological staining, allowed an accurate study of the sex chromosomal content and morphology of spermatozoa. In the males carrying an extra sex chromosome, we detected X- and Y-bearing spermatozoa in a ratio which did not differ significantly from the 1:1 ratio found in normal males. Aneuploidy for the sex chromosomes was found in approximately 15% of the spermatozoa of both XYY males and in 3% of the XXY male. The most striking finding was the relatively low percentage of spermatozoa in these patients, with an average of 65% in the XYY males and 84% in the XXY male. The other cells represented immature germ cells (IGC), including spermatogonia and spermatocytes arrested at various stages of spermatogenesis. Apparently, in XYY or XXY men, these IGC are shed into the semen to an increased extent as compared to normal, fertile men. The sex chromosome constitution of these IGC was heterogeneous. However, the finding that the majority of spermatozoa in semen of 47,XYY and 47,XXY males carried a single sex chromosome strengthens the hypothesis that a 46,XY germ cell line must be present, apparently with a proliferative advantage over the 47,XYY or 47,XXY cells.

Adult↗

Effect of oxygen concentration on in vitro fertilization and embryo culture in the human and the mouse.

OBJECTIVE: To compare the effect of culturing oocytes, zygotes and embryos under low (5%) versus ambient (20%) oxygen conditions on human IVF results and on mouse blastocyst formation. DESIGN: A prospective, randomized study of 257 consecutive IVF treatment cycles in 186 couples undergoing oocyte retrieval for various reasons of infertility. Gametes and resulting embryos after IVF were alternately allocated to fertilization and culture either under a gas phase of 5% CO2/90% N2/5% O2, or 5% CO2/95% air (20% O2). Oocytes and embryos from randomly bred and hybrid mouse strains were randomly allocated to culture under either of the two gas phases. SETTING: A university hospital-based IVF-ET program. MAIN OUTCOME MEASURE: In the human, rates of fertilization, embryonic development at the time of embryo replacement (42 to 46 hours after insemination), pregnancy, and implantation were compared. In the mouse, the rates of blastocyst formation were compared. RESULTS: Clinical pregnancies occurred in 24.2% versus 19.4% of retrievals when culture took place under low oxygen versus ambient oxygen conditions. Fertilization, embryonic development, pregnancy, and implantation rates did not differ significantly between the groups. Slightly higher blastocyst rates occurred when mouse embryos from hybrid strains were cultured under low oxygen compared with culture under ambient oxygen conditions, whereas no such difference in blastocyst rates was found in randomly bred mouse embryos. CONCLUSIONS: This study failed to demonstrate any improvement in human IVF results associated with the use of a gas mixture of 5% CO2/90% N2/5% O2 during the first two days of development compared with the use of 5% CO2 in air.

Animals↗

Chlamydia trachomatis antibody testing is more accurate than hysterosalpingography in predicting tubal factor infertility.

OBJECTIVE: To compare the likelihood of abnormal Chlamydia trachomatis antibody test results with that of abnormal hysterosalpingography (HSG) test results in patients with tubal factor infertility. DESIGN: Anti-C. trachomatis immunoglobulin G antibodies were determined prospectively in 211 consecutive infertility patients by means of an indirect fluorescent antibody technique. The results were compared with the results of HSG with respect to their predictive value of tubal factor infertility. Likelihood ratio calculations were used. SETTING: University hospital-based, tertiary care infertility clinic. PATIENTS: A series of 211 consecutive infertility patients. INTERVENTIONS: C. trachomatis antibody testing, HSG, laparoscopy. MAIN OUTCOME MEASURES: Likelihood ratios for abnormal C. trachomatis antibody test results and abnormal HSG results in infertility patients, as assessed by laparoscopy. RESULTS: The positive likelihood ratio for C. trachomatis antibody testing was 9.1, indicating a patient with tubal factor infertility to be 9.1 times more likely to have abnormal serology results than a patient without tubal factor infertility. This was superior to HSG, which had a positive likelihood ratio of 2.6 in our study and of 1.6 to 6.1 in the literature. The odds ratio of C. trachomatis antibody testing was 31.5 in our study. Its 90% confidence interval (8.3 to 138.5) did not overlap that of HSG as calculated from a meta-analysis of literature reports (5.3 to 7.9). CONCLUSIONS: C. trachomatis antibody testing is simple, inexpensive, and causes minimal inconvenience to the patient. It is more likely than HSG to be abnormal in patients with tubal factor infertility. C. trachomatis antibody testing deserves to become an integral component of the initial fertility work-up.

Antibodies, Bacterial↗

Modulation of embryonic Na(+)-K(+)-ATPase activity and mouse preimplantation development in vitro in media containing high concentrations of potassium.

The effect of various potassium concentrations (ranging from 1.4 mM to 30 mM K+) in modified Tyrode's medium on the culture of mouse zygotes obtained after in vitro fertilization to the blastocyst stage was examined. A clear dose-dependent negative effect of increasing K+ concentrations on the preimplantation embryonic development in vitro was found. We have previously shown that significantly more two-cell embryos reach the blastocyst stage when cultured during the second day postinsemination in medium supplemented with taurine. Because taurine, an amino acid that abounds in the reproductive tract, has been reported to inhibit the enzyme Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase), we used two other conditions known to inhibit the Na(+)-K(+)-ATPase to study their effect on mouse embryo development. Culturing embryos during a short period (the second day postinsemination) in low extracellular K+ concentrations (1.4 mM) or in medium supplemented with ouabain (50 microM) showed positive effects similar to those of culturing in medium with taurine (10 mM). This beneficial effect of ouabain was found in various K+ concentrations tested, including the high concentrations present in the oviduct. Although the effects of low K+ and taurine can possibly be ascribed to their other cellular effects, the effect of ouabain shows that inhibition of the Na(+)-K(+)-ATPase during the two-cell stage in the mouse is beneficial for further embryonic development to the blastocyst stage.

Analysis of Variance↗

Five different histological subtypes of germ cell malignancies in an XY female.

A case of a 19-year-old female with 46 XY gonadal dysgenesis and five different histological subtypes of germ cell malignancies is described. Both adnexa were removed, preserving the uterus. Pathology revealed gonadoblastoma with dysgerminoma differentiation present in both gonads and in the left gonad mature teratoma, embryonal carcinoma, and endodermal sinus tumor were identified as well. She received no adjuvant treatment and has remained well 30 months after diagnosis.

Adnexa Uteri↗

Immunohistochemical analysis of estrogen and progesterone receptors in fallopian tubes during ectopic pregnancy.

OBJECTIVE: To study decidualization, estrogen receptor (ER), and progesterone receptor (PR) expression in fallopian tubes containing an ectopic pregnancy (EP). DESIGN: Assessment of decidual reaction by light microscopy, staining of ER and PR in epithelium and stroma by immunohistochemical methods. SETTING: Academic hospital. PATIENTS: Twelve women with an ampullary located EP. INTERVENTION: A partial or complete tubal resection. RESULTS: Only minimal decidualization was observed in five tubes. Estrogen receptor expression was noted in glandular cells in seven tubes. No correlation was found between decidualization and ER staining. No PR expression was seen in glandular epithelium or in stroma. CONCLUSIONS: It is postulated that absence of PR is correlated to poor decidualization and to failure of treatment of EP with antiprogestins (RU486).

Decidua↗

Effect of the number of inseminated spermatozoa on subsequent human and mouse embryonic development in vitro.

It has been shown, in both human and mouse in-vitro fertilization (IVF), that an excess number of spermatozoa in the insemination medium leads to reduced fertilization rates. In this study, we evaluated human embryonic development after dividing the oocytes of each of 62 IVF attempts into two groups on the basis of insemination with two widely used concentrations (50,000 and 100,000 spermatozoa/ml). The embryonic growth was retarded in the group inseminated with 100,000 spermatozoa/ml: significantly fewer fast developing embryos (4-cell and 5- to 8-cell stages) were found (53.4% in the 100,000/ml group and 65.5% in the 50,000 group; P less than 0.05). In two experimental series, mouse embryonic development was evaluated in the presence of 0, 50,000, 100,000 and 500,000 spermatozoa per ml. In the first series, the spermatozoa were present during 5-20 h after insemination, while in the second series, the spermatozoa were present during the whole culture period of 120 h. The development of mouse embryos was impaired when 500,000/ml spermatozoa were present during the whole culture period. In contrast with human IVF results, the presence of up to 500,000 spermatozoa during the first 20 h after insemination did not have any significant detrimental effect on blastocyst formation in the mouse.

Animals↗

Lack of effect of peritoneal endometriosis on fertility in the rabbit model.

STUDY OBJECTIVE: To study the isolated influence of peritoneal endometrial implants on fertility in an adhesion-free rabbit model. STUDY DESIGN: Thirty-two rabbits with endometrium implants were used; 31 rabbits with fat implants served as controls. In these rabbits parameters of early embryonic development were investigated. RESULTS: No significant differences were noted in ovulation, ovum pick-up, fertilization, tubal transport, and embryonic and fetal development. CONCLUSION: In the adhesion-free rabbit model, peritoneal implants of endometriosis do not have an effect on fertility. This supports the contention that therapies focused toward the implants are unlikely to change the pregnancy outcomes. Alternatively, it may cast doubts onto the relevance of animal models in studying this disease.

Animals↗

Is there a solution for recurrent endometriosis?

Endometriosis may be either symptomatic or asymptomatic. Recurrence rates are mostly calculated on the basis of symptomatic patients re-presenting to their doctor. Based on the number of patients who experience recurrence of symptoms after medical or surgical therapy, recurrence rates of up to 45% after five years have been calculated. Whether the symptoms are due to real recurrence of disease or expanding, previously microscopic, endometriotic implants has not yet been established. Therapy should be tailored to the patient's complaints, but does not necessarily have to differ from that in patients with primary disease.

Dysmenorrhea↗

The impact of peritoneal trauma on intra-abdominal fibrinolytic activity, adhesion formation and early embryonic development in a rabbit longitudinal model.

Intra-abdominal adhesions may interfere with fertility following gynaecological surgery and injury to the peritoneum plays a central role in the pathogenesis. Tissue plasminogen activator and its antagonists play a pivotal role in the intra-abdominal balance between fibrinolysis and adhesion formation. This process may be cycle-dependent in women. In order to establish the impact of the fibrinolytic activity on adhesion formation after a standardized trauma, a rabbit longitudinal model was developed, which allowed the study of possible differences between the periods before and after ovulation. The influence of extra-genital adhesions on early embryonic development was investigated. No cycle-dependent changes in fibrinolytic activity of the peritoneal fluid (PF) or of the serum could be demonstrated. No correlation was found between post-operative adhesion formation and the fibrinolytic activity during surgery. Three weeks after surgery, a significant increase in fibrinolytic activity of the PF was observed. The rank order of sampling is suggested to account for these differences. Extra-genital adhesions did not markedly influence ovulation, ovum pick-up and fertilization in this hormonally controlled rabbit model.

Animals↗

A rabbit model of endometriosis.

Since not all problems in endometriosis can be studied in the human, there is need of an animal model. We transplanted endometrial tissue of the rabbit into the peritoneal cavity and studied the changes after 12 weeks. At that time the endometrial implants in the rabbit had become cystic structures. The macroscopic and histologic appearance was consistent with endometriosis. Hormonal supplementation turned out not to be necessary. Microsurgical techniques prevented the formation of tubo-ovarian adhesions. This makes the rabbit model suitable for studying the influence of endometrial implants on fertility.

Animals↗

Effect of endometriosis on early embryonic development in the rabbit.

The reasons for sub-fertility in patients with mild endometriosis remain unclear. Peritoneal fluid constituents may alter tubal transport and embryonic cleavage, with subsequent implantation disturbances. We used an animal model to study the influence of endometrial implants on early embryonic development. In 25 rabbits, endometrium from the right uterine horn was transplanted onto the peritoneum (Experimental group = Group E). In 25 rabbits, fat was transplanted (control group = group C). After a recovery period of 12 weeks the does were mated, and killed 24 h later. In the experimental group the implants had changed into cysts of 5-15 mm in diameter. Histological examination revealed endometrial glands and stroma in every specimen. Periadnexal adhesions did not develop in any animal. No marked differences were found between Groups E and C in embryonic cleavage stage, 24 h after mating. Additional culturing of the embryos for 48 h in a suitable culture medium revealed normal further development of the embryos. Bearing in mind the restrictions of extrapolating a rabbit model to the human, it is suggested that the decreased fecundity in mild endometriosis is not caused by altered early embryonic cleavage rate. The results of this study offer indirect evidence for implantation disturbances as a cause of endometriosis-associated sub-fertility.

Animals↗

Effect of endometriosis on ovulation, ovum pickup, fertilization and tubal transport in the rabbit.

In 25 rabbits (Group E) endometrium from the right uterine horn was transplanted onto the peritoneum. In 25 rabbits (Group C) fat was transplanted. After a recovery period of 12 weeks the does were mated, and killed 24 h later. In Group E the implants had changed into cysts of 5-15 mm in diameter. Histological examination revealed endometrial glands and stroma in every specimen. Periadenexal adhesions did not develop in any animal. No differences were found between Groups C and E in the number of corpora lutea, the recovery rate, the fertilization rate and the transport of fertilized ova. These findings indicate that endometrial implants in the rabbit have no influence on the ovulatory mechanisms, the pickup function of the oviduct, the fertilization rate or on the transport of fertilized ova. Taking into account the restrictions of a rabbit model, it is suggested that the decreased fecundity in mild endometriosis in the human may be caused by disturbances in post-fertilization events, i.e. development of the pre-implantation embryo or implantation.

Animals↗