Surrogacy: Ethical,legal, and social aspects

In considering the interrelated ethical, legal and social aspects of surrogacy we acknowledge that society has long accepted the delegation of various parental functions and explore the role of a surrogate in relationship to this as well as alluding to commoner comparisons with prostitution and adultery. In particular, the birth mother rule, the public antipathy to commercial surrogacy and restrictive legislation are explored and found to be inappropriate. It is concluded that the regulation, surveillance and assessment needed to ensure the best outcome for all concerned would perhaps be easiest achieved in programmes that are formally licensed under permissive legislation and adequately funded by commercial means.     

Expression of the inhibin/activin subunits alpha (α), beta-A (βA) and beta-B (βB) in benign human endometrial polyps and tamoxifen-associated polyps

Background Inhibins (INH) are dimeric glycoproteins, composed of an alpha subunit (INH-) and one of two possible beta subunits (INH-A or INH-B). They have substantial roles in human reproduction and in endocrine-responsive tumours. Therefore, the aims of this study were to determine the frequency and tissue distribution of INH-, INH-A and INH-B in normal human endometrium and glandular-cystic endometrial polyps, and polyps caused by tamoxifen use.Materials and methods Tissue samples were obtained from women in the proliferative, early secretory and late secretory phase as well as glandular-cystic polyps and endometrial polyps associated with tamoxifen use (n=5 each). Immunohistochemistry with specific monoclonal antibodies, a semi-quantitative analysis and statistical evaluation was performed.Results INH-, INH-A and INH-B were primarily observed in glandular and luminal epithelial cells, with a variant staining intensity in stromal cells. INH- in glands was significantly higher during the early secretory phase (p<0.05) and the late secretory phase (p<0.01) than in the proliferative phase with a significant difference between the early secretory and the late secretory phases (p<0.01). INH-A expression was significantly higher during the late secretory than the proliferative phase (p<0.05) and the late secretory than the early secretory phase (p<0.05), with no significant differences for INH-B. Glandular-cystic polyps showed significantly lower expression of INH- and INH-A than the late secretory endometria (p<0.05 and p<0.01 respectively). Additionally, tamoxifen-associated polyps also demonstrated a significantly lower expression of INH- and INH-A than late secretory endometria (p<0.01 and p<0.01 respectively). No statistical differences were observed between tamoxifen-associated and glandular-cystic polyps.Discussion INH-, INH-A and INH-B were expressed in normal endometrium and endometrial polyps. A cyclical expression of INH- and INH-A in normal glands may reflect a functional and hormone-dependent role in human endometrium. Significant differences in staining reaction between the late secretory endometria and polyps suggest that this tissue remains in the proliferating state rather than the secretory state. Therefore, endometrial polyps may be tumours of dysregulation with mainly proliferating characteristics, being unable to synchronise with normal endometrium.     

Routine laser assisted hatching results in significantly increased clincal pregnancies

Purpose: To elucidate the appropriateness of current indications for assisted hatching (AH) in cleavage stage human embryos and to confirm our preliminary findings that only young patients (about 67%) benefit from AH. Methods: Prior to transfer, 2 of 3 embryos selected for ET were subjected to laser assisted hatching (LAH). Control group consisted of patients matched by similar characteristics and protocol except LAH was not performed. Results: The clinical pregnancy rate in women 36 years was 64.9% (24/37) for embryos subjected to LAH but was significantly lower (p = 0.029) in the control (33.3%; 10/30). The implantation rate in women 36 years in the test group was 38.1% (40/105) that was significantly higher than that of the control group (17.5%, 14/80; p = 0.0039). Conclusions: LAH is beneficial for women 36 years but not for women 37 years, for embryos with thin zonae (16) but not with thick zonae (17), and for those with repeated failures (37–50%).     

Characterization and prediction of IVF cycles generating “slow-cleaving” embryos

Purpose To characterize and predict cycles generating slowcleaving embryos in in vitro fertilization, 86 cycles were retrospectively divided into two groups (slow, n=41, and fast, n=45 according to whether the number of blastomeres per embryo on day 3 was or > than the mean of the distribution, respectively.Results Cycles generating slowcleaving embryos were treated with luteinizing hormonereleasing hormone agonist before ovarian stimulation for a shorter period (12.1±0.5 versus 15.6±1.1 days; P0.01) and had higher immaturity grade of oocyte-corona-cumulus complexes which resulted in embryos (1.6±0.1 vs 1.3±0.1; P0.05) when compared to cycles producing fastcleaving embryos. Both variables entered in a logistic regression model applied in order to predict the probability of a cycle generating slowcleaving embryos (goodness-of-fit chisquare=180.0, degrees of freedom (df)=80, P=0.4786. This model predicted correctly 86.7% (13 of 15) of cycles generating slowcleaving embryos and 83.3% (10 of 12) of cycles producing fastcleaving embryos when the estimated probability of a cycle producing slowcleaving embryos was 0.7 or 0.3, respectively.Conclusion Shorter treatment with hormone-releasing hormone agonist before ovarian stimulation and higher immaturity grade of oocyte-corona-cumulus complexes which result in embryos are predictive characteristics of in vitro fertilization cycles generating slow-cleaving embryos.     

Morphology and X-ray microprobe analysis of spermatozoa from fertile and infertile men in in vitro fertilization

This paper reports differences observed in the elemental content of fertile and infertile human spermatozoa used in an in vitro fertilization (IVF) program. Fertile and infertile were designated by the successful penetration or failure to penetrate an oocyte in vitro. We report morphological and morphometric differences which, together with elemental changes, may be causes of infertility in apparently normal spermatozoa. There were significant differences (P<0.05) in sodium and chlorine concentrations between fertile and infertile samples and there was more chlorine than could be accounted for as sodium chloride. Many spermatozoa showed particles adhering to tails, with a higher incidence of contamination in the infertile spermatozoa. There were significant differences in both shapes of heads and lengths of tails between fertile and infertile spermatozoa.     

CIRS als Teil eines umfassenden Risikomanagements

Ohne ZusammenfassungDieser Beitrag wurde erstmals publiziert in chefarzt aktuell (Ausgabe 2/05). Abdruck mit freundlicher Genehmigung von chefarzt aktuell.     

The use of gonadotropin releasing hormone agonist (GnRHa) in good responders undergoing repeat in vitro fertilization/embryo transfer (IVF/ET)

The use of gonadotropin releasing hormone agonists (Gn-RHa) has been shown to improve the response in patients classified as poor responders undergoing ovarian stimulation for in vitro fertilization/embryo transfer (IVF/ET). This study sought to determine whether GnRHa therapy would benefit patients undergoing IVF/ET who had been classified as good responders in prior attempts. Twenty-three patients who had completed a prior IVF/ET attempt but who failed to conceive underwent ovarian stimulation using a combination of GnRHa and human menopausal gonadotropin (hMG). Each patient's prior stimulation served as her control and consisted of clomiphene citrate (CC)/hMG in 18 patients and follicle stimulating hormone (FSH) and/or hMG in 5 patients. The numbers of oocytes retrieved, oocytes fertilized, embryos cleaved, and embryos transferred were all significantly greater in cycles treated with GnRHa/hMG compared to control cycles. The clinical pregnancy rate was 39% and the ongoing pregnancy rate was 26% during the cycle when GnRHa pretreatment was utilized. These data suggest that GnRHa therapy is of benefit even to those patients previously classified as good responders undergoing ovarian stimulation for IVF/ET.Presented at the 45th Annual Meeting of the American Fertility Society, November 1989, San Francisco, California.     

Polycystic ovarian disease: Endocrinological parameters with specific reference to growth hormone and somatomedin-C

Summary Thirty-three women (22–38 years old) with polycystic ovarian disease (PCOD) were included in this study. The criteria for diagnosis were: an LH/FSH ratio greater than 2.0; polycystic ovaries, diagnosed by means of palpation and ultrasound; androgenism and menstrual cycle abnormalities. Using endocrine parameters, we attempted to define distinct forms of PCOD. The patients were placed in three groups according to serum levels of testosterone (T) and 17-hydroxyprogesterone (17 OHP) and the estrone/androstendione (E₁/⁴A) ratio. Patients in group I (n=18) had an elevated T level (>1.0 ng/ml) and a 17 OHP level under 4.0 ng/ml. This type of POCD was called the androgen type. Patients in group II (n=7) had normal T- and 17 OHP levels under 4.0 ng/ml and an elevated (E₁/⁴A) ratio. This type of PCOD was called the estrogen type. Group III (n=8) comprised patients with 17 OHP levels over 4.0 ng/ml. This type of PCOD was called the adrenocortical type. In two patients of this group, a modified ACTH test revealed late-onset congenital hyperplasia. The endocrine parameters of the patients with PCOD were compared with those of 17 adult without signs of PCOD. Statistical evaluation was done by variance analysis. Women with acromegaly often show signs of androgenism as well as menstrual cycle abnormalities. This may indicate an association between the growth factors human growth hormone (HGH) and somatomedin-C (Sm–C) and the biosynthese and metabolism of steroid hormone. Recent experiments have demonstrated such associations. Our study showed an association between the HGH and Sm–C levels and abnormal steroid hormone concentrations in women with androgen type PCOD (group I). These patients had a significantly decreased HGH level, a significantly decreased HGH/Sm–C ratio, and an increased average Sm–C level. These data suggest that elevated Sm–C levels can, by a negative-feedback mechanism, inhibit pituitary HGH production. We discuss the possible mechanisms causing elevation of plasma Sm–C, HGH, steroid hormones, excessive food intake, and possibly prolactin seem responsible for the clinical manifestation of increased Sm–C production in adolescence and for its level in the fertile years of patients.     

Beware: pregnancy and second-generation endometrial ablation

With the promotion of second-generation endometrial ablative techniques—namely thermal balloon endometrial ablation and microwave endometrial ablation—as alternatives to hysterectomy for dysfunctional uterine bleeding, with phrases like three-minute hysterectomy, some women become complacent about contraception after ablation. Some even assume that hysterectomy, as widely used in the popular press, means no more children. Pregnancy after endometrial ablation does not represent a failure of the technique. The failure is due to poor counselling or to women not taking the advice to use appropriate contraception after the procedure.     

Longitudinal Assessment of Ovarian Perifollicular and Endometrial Vascularity by Power Doppler Ultrasound in Pregnant and Non-Pregnant Cycles in the IVF Setting

Purpose: This longitudinal study aimed to compare ovarian perifollicular and endometrial blood flow (PFBF and EBF, respectively) during the follicular phase in pregnant and non-pregnant IVF cycles.Methods: Serial transvaginal scans were performed in 15 subjects undergoing IVF treatment. Both PFBF and EBF were subjectively graded (grades 0–4 for PFBF and grades 1–3 for EBF). After confirmation of clinical pregnancy, the treatment cycles were grouped into Pregnant and Non-pregnant cycles. Ovarian PFBF and EBF were retrospectively compared between the two groups.Results: In pregnant cycles, the proportion of large (15 mm) follicles with high (2–4) grade PFBF increased with time throughout the follicular phase, and the proportion of large follicles with poor (0–1) grade PFBF decreased. In non-pregnant cycles these trends were reversed. There was no difference in EBF between the two groups.Conclusion: The pattern of ovarian PFBF but not EBF may be predictive of treatment outcome.     

Reduced expression of alphavbeta3 integrin in the endometrium of unexplained infertility patients with recurrent IVF-ET failures: improvement by danazol treatment

Purpose : To determine whether there is any association between the expression of endometrial integrin v 3 and repeated IVF-ET failure and to examine the effect of danazol treatment on v 3 expression. Methods : This prospective study was performed using a semiquantitative immunohistochemical analysis on the staining intensity of v 3 in the mid-secretory endometria derived from 10 fertile women and 57 infertile patients with a history of repeated IVF-ET failures. Nine patients randomly selected from these 22 patients with unexplained infertility were then treated with oral danazol administration for 12 weeks and reexamined at the first mid-secretory phase after the danazol treatment. Result(s) : The levels of endometrial v 3 expression were lower in 22 patients with unexplained infertility than in the fertile control and 35 patients with explained infertility. The 9 patients treated with danazol showed a significant increase in the v 3 staining. Conclusion(s) : The significantly decreased expression of endometrial integrin v 3 suggested that functional, but not morphological, endometrial defect may be one of the causes for the patients with unexplained infertility. Danazol may have a therapeutic potential in improving endometrial function together with up-regulation of v 3.     

The association between chlamydial-specific IgG and IgA antibodies and pregnancy outcome in an in vitro fertilization program

Chammydial-specfic IgG and IgA antibodies were determined by a single serovar (L2) immunoperoxidase assay (IPA) in the serum of all patients that have conceived in an in vitro fertilization and embryo transfer (IVF & ET) progrom (n=106) and in a group of patients that went through the program at the same period of time and did not conceive (n=94). The prevalence rate of elevated IPA IgG (titers1128) and IPA IgA (titers116) specific to chlamydiae was significantly higher (P<0.001) in the IVF&ET pregnancy loss and nonconception groups (failures) versus the IVF&ET term pregnancy group (successes) (74 vs 47%, odds ratio=4.1, and 34 vs 14%, odds ratio=4.3, respectively). Stepwise discriminant analysis revealed that elevated specific chlamydial IgG had the greatest effect on the variance between successes and failures in this study group. Our study indicates the possible role of past or chronic active chlamydiae infection on the take-home baby rate in an IVF&ET program.     

Identifying the Public’s Knowledge and Intention to Use Human Cloning in Greek Urban Areas

Purpose: The understanding of the publics knowledge on human cloning (HC) and its acceptability are considered important for the development of evidence-based policy making. The aim of this research study was to investigate the demographic and socioeconomic variables that affect the publics knowledge and intention to use HC in urban areas of Greece. Additionally, the possible association of religiousness with the knowledge and the intention to use HC were also investigated.Methods Individual interviews were conducted with 1020 men and women of urban areas in Greece. Stratified random sampling was performed to select the respondents. Several scientists, experts in HC, evaluated the content of the instrument initially developed. The final questionnaire was consequently the result of a pilot study.Results Almost half of the respondents (51.5%) believed that HC is a sort of in vitro fertilization and 42.9% that it has already been applied to human being. They were not aware that the cloned fetus grows in the womans uterus (41.5%) and that HC could regenerate human organs (41.7%). The acceptability of human cloning for the cure of terminal diseases and transplantation need is very high (70.7% and 58.6%, respectively). The publics intention to have recourse to cloning on the grounds of bringing back to life a loved person or because of reproductive disorders was reported as desire by 35% and 32.5%, respectively. The occupational category (scientists, self-employed, and artists), the Intention to use HC, and the number of children are highly significant predictors of valid knowledge about HC. Low rates of church attendance appeared to relate with high reported Intention to use HC, and increasing scores of valid knowledge about HC increased the publics Intention to use HC.Conclusions A number of specific demographic and socioeconomic characteristics and high scores of knowledge provide a persuasive justification in demonstrating intention toward HC. The current study suggests that these findings should receive further attention by policymakers and scientists within the Greek context.     

Mixed germ cell tumor of the ovary mimicking unruptured ectopic pregnancy presenting with unusually high serum alpha-fetoprotein level

Malignant germ cell tumors of the ovary constitute fewer than 5% of all ovarian cancers. Malignant mixed germ cell tumors (MMGCTs) may secrete tumor markers including -fetoprotein (AFP) and -human chorionic gonadotropin (-hCG) depending on the type of tumor cells. Because these tumors are almost always seen in the reproductive period, their differential diagnosis with -hCG secreting ectopic pregnancy is of importance. The patient with MMGCT may present with abdominal pain, vaginal bleeding and pelvic mass similar to an ectopic pregnancy. Here, we present a case of MMGCT, which was referred to our clinic with the admission diagnosis of ectopic pregnancy. However, serum AFP level was exceedingly high (2,172 IU/ml), and transvaginal ultrasonography demonstrated an atypical solid mass 6 cm in diameter. As a result, a hormonally active germ cell tumor of the ovary needed to be considered in the differential diagnosis of ectopic pregnancy.     

A controlled ovarian hyperstimulation regimen involving intermittent gonadotropin administration with a “short” protocol of gonadotropin releasing hormone agonist for in vitro fertilization

Purpose: To examine the effects of an intermittent injection regimen of exogenous gonadotropin for controlled ovarian hyperstimulation on follicular development and on in vitro fertilization (IVF) outcome, 120 women who were candidates for IVF received intermittent injection (II) or consecutive injection (CI) regimens with a short protocol (SP) or a long protocol (LP) of gonadotropin releasing hormone agonist (GnRHa). Pure follicle stimulating hormone (pFSH) was injected to the women in the II groups on the first, second, and fifth days of the stimulation cycle and every other day thereafter. The women in the CI groups received a daily injection of pFSH. An additional 16 patients who were treated with both II-SP and CI-LP were also analyzed. Results: Although the cancellation rate in the II-LP group was higher than those in the other groups, follicular development and IVF outcomes in the II-SP group were similar to those in the CI groups. The number of injections in the II-SP group was about half that in the CI groups. Conclusions: These results indicate that an intermittent pFSH injection regimen with a short protocol of GnRHa may be beneficial for patients in terms not only of being a less painful treatment but also causing less physical and mental stress than daily injections.     

The relation between depth of trophoblastic invasion and β-HCG levels in tubal pregnancies

-HCG (human chorionic gonadotropin) values of over 2500 I.U./l are associated with higher failure rates for therapy with prostaglandin F2 alpha in tubal pregnancies. The purpose of our study was to ascertain if the 2500 I.U./l limit correlates with histopathology. We therefore compared the pre-operative -HCG-values and intraluminal and extraluminal trophoblast growth in tubal pregnancy. Purely intraluminal trophoblast was significantly more frequent in patients of group I (-HCG < 2500 I.U./1), while group II patients (-HCG > 2500 I.U./l.) almost exclusively had extraluminal growth (P=0.0045). Since the efficacy of prostaglandin F2 alpha therapy depends on intact tubal musculature the correlation of the -HCG threshold level with histopathologic findings may explain the high failure rate in patients with -HCG values above 2500 I.U./l. Correspondence to: M. Klein     

Patterns of increase in serum estradiol in response to ovarian stimulation and their relationship to oocyte fertilization and cleavage in vitro

The in vitro fertilization and cleavage rates of oocytes obtained from patients exhibiting two different patterns of increase in serial serum concentrations of estradiol (E₂) in response to ovarian stimulation were compared. Forty-two cycles (from 38 stimulated patients) were evaluated because they fulfilled requirements from two predefined patterns of E₂ response to ovarian stimulation. In 16 cycles, serial serum E₂ concentrations followed a plateau pattern (group A), viz., the rate of increase in the serum concentration of E₂ decreased prior to the administration of human chorionic gonadotropin (hCG). In 26 cycles, serial serum E₂ concentrations followed a leap pattern (group B), in which the rate of increase in serum concentrations of E₂ increased progressively up to and including the day of hCG administration. There was no significant difference in the fertilization rate of oocytes obtained from patients exhibiting either pattern A or pattern B (78 versus 74%) but the cleavage rate was significantly higher in ova obtained from patients who exhibited pattern A rather than pattern B (72 vs 50%; P 0.01). In addition, embryos resulting from fertilized ova obtained from women in group A were of better quality morphologically than those obtained from women in group B (mean embryo grades, 3.9 vs 3.2; P 0.005). We conclude that cycles in which serial serum concentrations of E₂ follow pattern A in response to stimulation give rise to oocytes that, when fertilized, yield higher cleavage rates and better-quality embryos than oocytes obtained from women in whom serial serum E₂ concentrations follow pattern B. This finding is in keeping with the hypothesis that plateau and leap patterns of serial serum E₂ concentrations are reflective of synchronous and asynchronous follicular recruitment, respectively.     

ANDROLOGY: Relationships Between Sperm Motility Characteristics Assessed by the Computer-Aided Sperm Analysis (CASA) and Fertilization Rates In Vitro

Purpose: Some studies have suggested that computer-aided sperm analysis (CASA) estimates of concentration and movement characteristics of progressively motile spermatozoa are related to fertilization rates in vitro. However, it has also been suggested that the greater number of motility parameters assessed by CASA does not imply more precision in predicting fertility. This study was carried out to investigate the relationships between the CASA estimates and fertilization rates in vitro.Methods: Semen quality analysis was performed using CASA in 136 in vitro fertilization-embryo transfer (IVF-ET) cycles with at least 3 oocytes collected. The CASA estimates before and after swim-up were compared between 108 cycles with fertilization rate >50% (good group) and 28 cycles with fertilization rate 50% (poor group).Results: Before swim-up, there were significant correlations between fertilization rates and CASA estimates, including amplitude of lateral head displacement (ALH) (r = .269), curvilinear velocity (VCL) (r = .297), straight line velocity (VSL) (r = .266), and rapid sprm movement (Rapid) (r = .243). There was also a significant correlation between the fertilization rates and straightness (STR) after swim-up (r = –0.178). As for sperm movement characteristics, there were significant differences of ALH (p < .005), VCL (p < .001), VSL (p < .005), and Rapid (p < .01) between good and poor groups before swim-up. After swim-up, there were significant differences of VCL (p < .005), average path velocity (VAP) (p < .005), and Rapid (p < .05) between the two groups.Conclusions: These results indicate that some of the CASA estimates provide reliable estimation of the fertilizing ability of human sperm. There were significant differences of the two sperm movement characteristics, including VCL and Rapid (before and after swim-up), indicating that the total distance traveled by rapid sperm movement might be important in human sperm fertilizing abilities.     

There is a cutoff limit in diameter between a blastomere and a small anucleate fragment

Purpose : To document the DNA content of blastomeres/fragments from early human preembryos and to determine if there is a cutoff diameter at which a cell should be consi- dered an anucleate fragment rather than a blastomere. Methods : Surplus embryos from in vitro fertilization were used. Individual cells were measured, fixated, and stained for DNA. Results : In day 2 preembryos, only 2% of cells with a diameter <45 m contained DNA, compared with 67% of those 45 m. In day 3 preembryos, 3% of cells <40 m contained DNA, compared with 66% of those 40 m. Conclusions : It is suggested that cells <45 m in day 2 preembryos, and <40 m in day 3 preembryos should be classified as fragments, and cells larger than this, as blastomeres. This may influence the embryo scoring system for in vitro fertilization. We therefore recommend that cells within this critical range should be measured when scoring preembryos for embryo transfer.