During implantation, the embryo adheres to the endometrium via cell adhesion molecules (CAMs) present on blastocyst trophectoderm and endometrial epithelial cells. CAMs, including integrins and extracellular matrix (ECM) ligands, are most likely regulated by hormones, cytokines and growth factors. We hypothesized first that activin A affects the adhesive properties of trophoblast cells and second that alterations in dimeric activin A levels in the uterine cavity could disrupt adhesion, thereby causing implantation failure.
METHODS
This study examined effects of activin A on trophoblast cell adhesion and measured activin A levels in secretory phase uterine washings from women with and without endometriosis (EOS). Activin receptor expression on trophoblast (HTR8) cells was examined by RT–PCR, and adhesive molecules measured by integrin antibody and cell–matrix adhesion assays. Dimeric activin A was measured (enzyme-linked immunosorbent assay) in uterine washings (14 controls and 23 EOS), and βA-subunit localization was verified in endometrial tissues.
RESULTS
Activin receptors are expressed by HTR8 cells. Activin A activated Smad2 in a concentration-dependent manner which was blocked by an activin receptor inhibitor (SB431542). Following activin A treatment (50 ng/ml for 24 h), trophoblast cell surface integrins 1 2 3 5, β1, β2, β4 and vβ5 were decreased, as was cell binding to the ECM ligands, fibronectin, collagen IV and collagen I (P < 0.05). Activin A was detected in 56.5% of EOS and 21.4% of control washings, with measured levels from 42 to 8481 pg/ml (not significantly different).
CONCLUSIONS
Decreased trophoblast CAM production and adhesion could be caused by dysregulated local activin A levels and may contribute to implantation failure. This could explain, in part, the infertility observed in women with EOS.
The aim of this study was to evaluate protein expression profile and quantify the proteins present in follicular fluid (FF) samples from women with endometriosis and pregnant women without endometriosis.
METHODS
A prospective case–control study was carried out including women with Stage III or IV endometriosis (Group I) and pregnant women without endometriosis (Group II), both at the maximum age of 35 years. Women were submitted to controlled ovarian stimulation for in vitro fertilization, and FF was collected after ultrasound-guided ovarian aspiration. FF from both ovaries was pooled, and patient samples were pooled according to Group I or II. Pooled protein samples were separated and analyzed by MudPIT (multidimensional protein identification technology followed by ExpressionE and label-free quantification with ProteinLynxGlobalServer 2.4v, IdentityE and ExpressionE software).
RESULTS
A total of 416 proteins or randomic sequence were identified, 62 proteins differentially expressed between Groups I and II. One (1.6%) was expressed at a higher level and 36 (58.1%) were uniquely expressed in Group I, whereas 8 (12.9%) were expressed at a higher level and 17 (27.4%) were uniquely expressed in Group II. Of all these, 15 (24.2%) are related to binding, 1 (1.6%) to immune response, 8 (12.9%) to cell division, 3 (4.8%) to cellular metabolism, 16 (25.8%) to general function and 19 (30.6%) do not yet present an identified function.
CONCLUSIONS
Protein expression profiles of patients with and without endometriosis identified at least 64 proteins differentially expressed, which may be related to the physiopathology of endometriosis. These proteins may additionally be useful in determining potential biomarkers for diagnostics, as well as for therapeutic intervention in women with infertility due to endometriosis.
Female cancer patients are offered ‘banking’ of gametes before starting fertility-threatening cancer therapy. Transplants of fresh and frozen ovarian tissue between healthy fertile and infertile women have demonstrated the utility of the tissue banked for restoration of endocrine and fertility function. Additional methods, like follicle culture and isolated follicle transplantation, are in development.
METHODS
Specialist reproductive medicine scientists and clinicians with complementary expertise in ovarian tissue culture and transplantation presented relevant published literature in their field of expertise and also unpublished promising data for discussion. As the major aims were to identify the current gaps prohibiting advancement, to share technical experience and to orient new research, contributors were allowed to provide their opinioned expert views on future research.
RESULTS
Normal healthy children have been born in cancer survivors after orthotopic transplantation of their cryopreserved ovarian tissue. Longevity of the graft might be optimized by using new vitrification techniques and by promoting rapid revascularization of the graft. For the in vitro culture of follicles, a successive battery of culture methods including the use of defined media, growth factors and three-dimensional extracellular matrix support might overcome growth arrest of the follicles. Molecular methods and immunoassay can evaluate stage of maturation and guide adequate differentiation. Large animals, including non-human primates, are essential working models.
CONCLUSIONS
Experiments on ovarian tissue from non-human primate models and from consenting fertile and infertile patients benefit from a multidisciplinary approach. The new discipline of oncofertility requires professionalization, multidisciplinarity and mobilization of funding for basic and translational research.
Although prescription drug use is common during pregnancy, the human teratogenic risks are undetermined for more than 90% of drug treatments approved in the USA during the past decades. A particular birth defect may have its origins through multiple mechanisms and possible exposures, including medications. A specific pathogenic process may result in different outcomes depending upon factors such as embryonic age at which a drug is administered, duration and dose of exposure and genetic susceptibility. This review focuses on the teratogenic mechanisms associated with a number of medications.
METHODS
We used three methods to identify the teratogenic mechanisms of medications: the MEDLINE and EMBASE databases, two recent books on teratogenic agents and a list of drugs classified as U.S. Food and Drug Administration class D or X. Mechanisms were included only if they are associated with major structural birth defects and medications that are used relatively frequently by women of reproductive age.
RESULTS
We identified six teratogenic mechanisms associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption and specific receptor- or enzyme-mediated teratogenesis. Many medications classified as class X are associated with at least one of these mechanisms.
CONCLUSIONS
Identifying teratogenic mechanisms may not only be relevant for etiologic and post-marketing research, but may also have implications for drug development and prescribing behavior for women of reproductive age, especially since combinations of seemingly unrelated prescription and over the counter medications may utilize similar teratogenic mechanisms with a resultant increased risk of birth defects.
Timing of natural menopause has great implications for fertility and women's health. Age at natural menopause (ANM) is largely influenced by genetic factors. In the past decade, several genetic studies have been conducted to identify genes in ANM, which can help us unravel the biological pathways underlying this trait and the associated infertility and health risks. After providing an overview of the results of the genetic studies performed so far, we give recommendations for future studies in identifying genetic factors involved in determining the variation in timing of natural menopause.
METHODS
The electronic databases of Pubmed and Embase were systematically searched until September 2009 for genetic studies on ANM, using relevant keywords on the subject. Additional papers identified through hand search were also included.
RESULTS
Twenty-eight papers emerged from our literature search. A number of genetic regions and variants involved in several possible pathways underlying timing of ANM were identified, including two possible interesting regions (9q21.3 and chromosome 8 at 26 cM) in linkage analyses. Recent genome-wide association studies have identified two genomic regions (19q13.42 and 20p12.3), containing two promising candidate genes (BRKS1 and MCM). In the candidate gene association studies on ANM, very few consistent associations were found.
CONCLUSION
A number of genetic variants have been discovered in association with ANM, although the overall results have been rather disappointing. We have described possible new strategies for future genetic studies to identify more genetic loci involved in the variation in menopausal age.
Previous research has demonstrated an association between economic contraction at both the individual and aggregate level, and adverse health outcomes. Proposed mechanisms include increased psychosocial stress and loss of resources. The aim of this review is to assess the quantity, validity and consistency of empirical evidence examining economic contraction and birth outcomes.
METHODS
Empirical, English-language articles examining the effects of economic change at either the aggregate or individual level on birthweight, length of gestation, neonatal mortality and the secondary sex ratio were identified using PubMed and ISI Web of Knowledge. Studies were organized by level of analysis and birth outcome and evaluated for internal and external validity.
RESULTS
One individual-level study reported a strong association between individual shift to inadequate employment and decreased birthweight. Of seven aggregate-level studies on birthweight, five exhibited moderate to strong validity but reported inconsistent findings. Similarly, findings from five studies (four with moderate to strong validity) examining rates of neonatal mortality reported inconsistent findings. Three of four moderate to strong studies reported a reduced secondary sex ratio following economic contraction.
CONCLUSIONS
Associations between economic contraction and birthweight, neonatal mortality and the secondary sex ratio remain speculative. Consensus on methodology is needed to compare findings across studies. Further research on economic contraction and the secondary sex ratio, as well as individual-level birthweight and length of gestation, is warranted.
An ectopic pregnancy is a pregnancy which occurs outside of the uterine cavity, and over 98% implant in the Fallopian tube. Tubal ectopic pregnancy remains the most common cause of maternal mortality in the first trimester of pregnancy. The epidemiological risk factors for tubal ectopic pregnancy are well established and include: tubal damage as a result of surgery or infection (particularly Chlamydia trachomatis), smoking and in vitro fertilization. This review appraises the data to date researching the aetiology of tubal ectopic pregnancy.
METHODS
Scientific literature was searched for studies investigating the underlying aetiology of tubal ectopic pregnancy.
RESULTS
Existing data addressing the underlying cause of tubal ectopic pregnancy are mostly descriptive. There are currently few good animal models of tubal ectopic pregnancy. There are limited data explaining the link between risk factors and tubal implantation.
CONCLUSIONS
Current evidence supports the hypothesis that tubal ectopic pregnancy is caused by a combination of retention of the embryo within the Fallopian tube due to impaired embryo-tubal transport and alterations in the tubal environment allowing early implantation to occur. Future studies are needed that address the functional consequences of infection and smoking on Fallopian tube physiology. A greater understanding of the aetiology of tubal ectopic pregnancy is critical for the development of improved preventative measures, the advancement of diagnostic screening methods and the development of novel treatments.
In the first trimester the extravillous cytotrophoblast cells occlude the uterine spiral arterioles creating a low oxygen environment early in pregnancy, which is essential for pregnancy success. Paradoxically, shallow trophoblast invasion and defective vascular remodelling of the uterine spiral arteries in the first trimester may result in impaired placental perfusion and chronic placental ischemia and hypoxia later in gestation leading to adverse pregnancy outcomes. The hypoxia inducible factors (HIFs) are key mediators of the response to low oxygen. We aimed to elucidate mechanisms of regulation of HIFs and the role these may play in the control of placental differentiation, growth and function in both normal and pathological pregnancies. The Pubmed database was consulted for identification of the most relevant published articles. Search terms used were oxygen, placenta, trophoblast, pregnancy, HIF and hypoxia. The HIFs are able to function throughout all aspects of normal and abnormal placental differentiation, growth and function; during the first trimester (physiologically low oxygen), during mid-late gestation (where there is adequate supply of blood and oxygen to the placenta) and in pathological pregnancies complicated by placental hypoxia/ischemia. During normal pregnancy HIFs may respond to complex alterations in oxygen, hormones, cytokines and growth factors to regulate placental invasion, differentiation, transport and vascularization. In the ever-changing environment created during pregnancy, the HIFs appear to act as key mediators of placental development and function and thereby are likely to be important contributors to both normal and adverse pregnancy outcomes.
The quantity and the reasons for seeking cross border reproductive care are unknown. The present article provides a picture of this activity in six selected European countries receiving patients.
METHODS
Data were collected from 46 ART centres, participating voluntarily in six European countries receiving cross border patients. All treated patients treated in these centres during one calendar month filled out an individual questionnaire containing their major socio-demographic characteristics, the treatment sought and their reasons for seeking treatment outside their country of residence.
RESULTS
In total, 1230 forms were obtained from the six countries: 29.7% from Belgium, 20.5% from Czech Republic, 12.5% from Denmark, 5.3% from Slovenia, 15.7% from Spain and 16.3% from Switzerland. Patients originated from 49 different countries. Among the cross border patients participating, almost two-thirds came from four countries: Italy (31.8%), Germany (14.4%), The Netherlands (12.1%) and France (8.7%). The mean age of the participants was 37.3 years for all countries (range 21–51 years), 69.9% were married and 90% were heterosexual. Their reasons for crossing international borders for treatment varied by countries of origin: legal reasons were predominant for patients travelling from Italy (70.6%), Germany (80.2%), France (64.5%), Norway (71.6%) and Sweden (56.6%). Better access to treatment than in country of origin was more often noted for UK patients (34.0%) than for other nationalities. Quality was an important factor for patients from most countries.
CONCLUSIONS
The cross border phenomenon is now well entrenched. The data show that many patients travel to evade restrictive legislation in their own country, and that support from their home health providers is variable. There may be a need for professional societies to establish standards for cross border reproductive care.
In this article, we discuss sex selection not intended to help a couple avoid having a child with a severe genetic disorder, but to avoid possible health risks further along the line of generations. Sex selection may be put to this use in the context of preventing mitochondrial DNA disorders by means of preimplantation genetic diagnosis (PGD) and possibly in the future also through nuclear transfer (NT; also known as mitochondrial gene replacement). A relevant analogy can be found in the context of PGD for X-linked diseases, where sex selection against healthy female carrier embryos would have the same 2-fold purpose of (i) avoiding difficult reproductive decisions for the future child and (ii) avoiding transmission of the mutation to a possible third generation. Because sex selection would still be done for reasons of health, this application should not give rise to the moral concerns associated with sex selection for non-medical reasons. However, the proportionality of adding the relevant procedures to PGD or NT is a relevant concern. We discuss post- and preconceptional sex selection strategies. We conclude that if PGD is already part of the procedure, either as the central technology or as a back-up test after NT, preferentially transferring male embryos could in principle be a morally acceptable way of reducing possible burdens and risks. To start an IVF/PGD-cycle especially for this purpose would be disproportional. The alternative approach of preconceptional sex selection may be morally justified as a means to increase the chances of obtaining male embryos.
Since Carlsen and co-workers reported in 1992 that sperm counts have decreased during the second half of the last century in Western societies, there has been widespread anxiety about the adverse effects of environmental pollutants on human fecundity. The Carlsen report was followed by several re-analyses of their data set and by many studies on time trends in sperm quality and on secular trends in fecundity. However, the results of these studies were diverse, complex, difficult to interpret and, therefore, less straightforward than the Carlsen report suggested. The claims that population fecundity is declining and that environmental pollutants are involved, can neither be confirmed nor rejected, in our opinion. However, it is of great importance to find out because the possible influence of widespread environmental pollution, which would adversely affect human reproduction, should be a matter of great concern triggering large-scale studies into its causes and possibilities for prevention. The fundamental reason we still do not know whether population fecundity is declining is the lack of an appropriate surveillance system. Is such a system possible? In our opinion, determining total sperm counts (as a measure of male reproductive health) in combination with time to pregnancy (as a measure of couple fecundity) in carefully selected populations is a feasible option for such a monitoring system. If we want to find out whether or not population fecundity will be declining within the following 20–30 years, we must start monitoring now.
Innovative imaging techniques, using up-to-date ultrasonic equipment, necessitate specific biometry. The aim of our study was to test the possibility of detailed human embryonic biometry using a virtual reality (VR) technique.
METHODS
In a longitudinal study, three-dimensional (3D) measurements were performed from 6 to 14 weeks gestational age in 32 pregnancies (n = 16 spontaneous conception, n = 16 IVF/ICSI). A total of 125 3D volumes were analysed in the I-Space VR system, which allows binocular depth perception, providing a realistic 3D illusion. Crown-rump length (CRL), biparietal diameter (BPD), occipito-frontal diameter (OFD), head circumference (HC) and abdominal circumference (AC) were measured as well as arm length, shoulder width, elbow width, hip width and knee width.
RESULTS
CRL, BPD, OFD and HC could be measured in more than 96% of patients, and AC in 78%. Shoulder width, elbow width, hip width and knee width could be measured in more than 95% of cases, and arm length in 82% of cases. Growth curves were constructed for all variables. Ear and foot measurements were only possible beyond 9 weeks gestation.
CONCLUSIONS
This study provides a detailed, longitudinal description of normal human embryonic growth, facilitated by a VR system. Growth curves were created for embryonic biometry of the CRL, BPD, HC and AC early in pregnancy and also of several ‘new’ biometric measurements. Applying virtual embryoscopy will enable us to diagnose growth and/or developmental delay earlier and more accurately. This is especially important for pregnancies at risk of severe complications, such as recurrent late miscarriage and early growth restriction.
It would be of value to identify ongoing spermatogenesis molecular markers which can predict successful sperm recovery in patients with non-obstructive azoospermia undergoing conventional or microsurgical testicular sperm extraction (TESE/microTESE). ESX1 is an X-linked homeobox gene expressed in testis, placenta, brain and lung in humans and specifically in pre- and post-meiotic germ cells of the testis in mice.
METHODS
We investigated the sequence, expression (by RT–PCR) and epigenetic status (by promoter pyrosequencing) of ESX1 in testicular tissue samples, obtained from 81 azoospermic subjects in the context of surgical sperm extraction, to check a possible association between ESX1 alterations and impaired spermatogenesis, as determined by histological analysis.
RESULTS
The ESX1 transcript was detected in 100% of cases diagnosed as obstructive azoospermia (33), hypospermatogenesis (18) and incomplete maturation arrest (MA) (2), and sperm recovery was also successful in 100% of these cases. ESX1 mRNA was also detected in 5 of 6 patients with incomplete Sertoli cell-only syndrome, in 4 of 6 subjects with complete MA but in only 3 of 16 cases of complete Sertoli cell-only syndrome (cSCOS), whereas sperm recovery was successful in 4 of 6, 2 of 6 and 5 of 16 of these patients, respectively. In cases of focal spermatogenesis, ESX1 expression and sperm retrieval were concordant in 14 of 19 (74%) cases subjected to TESE, but in only 3 of 11 (27%) men who underwent microTESE. With TESE, but not with microTESE, both samples originated from adjacent testicular areas. The pyrosequencing of the ESX1 CpG island revealed methylation levels that were significantly lower in ESX1 expressors when compared with non-expressors.
CONCLUSIONS
ESX1 emerges as a potentially reliable spermatogenesis molecular marker, whose clinical value as a predictor of successful sperm retrieval warrants further studies.
Assessment of sperm morphology (including morphometry) is extensively used to determine one of the qualities of a semen sample and depends on the differential staining of spermatozoa. A staining technique should cause as little change to sperm dimensions and form as possible in order to reliably evaluate the morphometric features of the sperm. Various staining techniques have been employed, but only a few have been recommended by the World Health Organization and are amenable to automated sperm morphometry analysis. Our study was aimed at comparing the effect of three staining techniques [Papanicolaou (PAP), Rapidiff® (RD) and SpermBlue® (SB)] on human sperm head dimensions and to compare these with the head dimensions in fresh semen.
METHODS
Smears made from human semen samples (n = 24) were stained according to the three staining techniques and sperm head morphometry was assessed with the Sperm Class Analyzer. Head dimensions of fresh spermatozoa were measured with a digital calliper on a computer screen. The minimum number of spermatozoa to be analyzed to represent the sperm population and the degree of inter-laboratory variation were determined. Electron micrographs from the same semen samples were used to determine the actual acrosome coverage of the spermatozoa in the semen (n = 7) in order to verify the results of the automatic analyses.
RESULTS
The osmolality of human semen differs from that of the RD and PAP fixatives and stains, but is more similar to the SB fixative and stain. At least 100 spermatozoa should be analyzed to include a representative sample of the sperm population. RD caused sperm heads to swell, PAP caused them to shrink and SB had no significant effect on sperm head dimensions when compared with spermatozoa in fresh semen. Very little inter-laboratory variations were found. The percentage acrosome coverage was significantly different between the three staining techniques, as well as between the RD and PAP stains and the manual measurements obtained using the electron micrographs.
CONCLUSIONS
Different staining techniques change the morphometric dimensions of the human sperm head, probably due to the fact that either the fixatives or stains are not iso-osmotic in relation to human semen. Since these changes in sperm head dimensions are not uniform, care should be taken when selecting a staining technique. Ideally, stained spermatozoa should have dimensions as close to spermatozoa in fresh semen as possible, as was found with the SB staining method, resulting in accurate evaluations of sperm head morphometry.
Consecutive use of the levonorgestrel-releasing intrauterine system (LNG-IUS) is increasing. However, little is known about factors that predict the bleeding during consecutive use. The objective of this study was to analyse the possible factors which may predict the bleeding pattern during the first year of use of a second LNG-IUS.
METHODS
Fertile-aged women (n = 204) who had used their first LNG-IUS for over 4 years and who opted for a second LNG-IUS were recruited. Bleeding data were reported using 90-day reference periods (RPs) starting from the last 90 days of the first LNG-IUS use (baseline), until the end of the first year of the second LNG-IUS (RPs 1–4).
RESULTS
Demographic factors such as age, parity, body mass index, indication of LNG-IUS use or smoking could not be identified as predictors for bleeding and spotting (B/S). Mean (±SD) number of B/S days was 8.9 (±9.1) at baseline. This increased slightly during RP1 and fell to 6.4 (±8.1) during RP4. Compared with the mean, women with uterine fibroids or a bleeding pattern of >9 days of spotting or any bleeding at RP1 had more B/S days during RP1–4. Although the number of B/S days decreased progressively from RP1 to RP4 in the group with a bleeding pattern of >9 days of spotting or any bleeding at baseline, such a phenomenon was not observed for women with fibroids. The difference for the change in B/S days between women with and without fibroids was statistically significant at RP3 and RP4. A high degree (91.7%) of satisfaction with the bleeding pattern was observed, with amenorrhoeic women being most satisfied.
CONCLUSIONS
Uterine B/S is reduced during consecutive use of the LNG-IUS. Women with uterine fibroids or any bleeding at baseline continued to have more B/S than other women.
There is a need to improve our understanding of contraceptive use over the long term. The aims of this study were to describe contraceptive use and pregnancies in the same women followed prospectively from 19 to 44 years of age.
METHODS
In 1981, a postal questionnaire about contraception, pregnancies and reproductive health was sent to a random sample (n = 656) of 19-year-old women resident in Gothenburg, Sweden. The responders were contacted again every fifth year.
RESULTS
At 19 years of age, 74% of the women had already used contraception and this increased to 98% at 44 years. Combined oral contraception was the commonest method currently used up to 29 years of age (48/51/22% at 19/24/29 years of age, respectively) and thereafter an intrauterine device (IUD: 34/39/38% at 34/39/44 years of age, respectively). Condom use alone during the 25-year study period was: 14/12/24/21/21/15% and non-use of contraception was: 35/24/26/20/21/26%. The mean number of pregnancies/children increased from 0.2/0.1 at 19 years of age to 3.1/2.1 at 44 years. Women who had been pregnant and women who had not been pregnant ≤19 years of age were compared up to 44 years of age (months of OC use: 69/107, P < 0.01; months of IUD use: 126/91, P < 0.01; 4.2/2.9 pregnancies, P < 0.001; 2.5/2.1 children, P< 0.09).
CONCLUSIONS
Choice of contraception was strongly related to age and parity, and the cumulative total number of pregnancies at 44 years of age, and contraceptive choice was related to age at first pregnancy.
Carrier status of a structural balanced chromosome abnormality is associated with recurrent miscarriage. There is, at present, no evidence of the impact of the sequence of preceding pregnancies on the probability of carrier status. The aim of our study was therefore to examine whether the history of consecutive versus non-consecutive miscarriages in couples with two or more miscarriages has any impact on the probability of carrying a chromosome abnormality.
METHODS
A nested case–control study was performed in six centres for clinical genetics in the Netherlands. Couples referred for chromosome analysis after two or more miscarriages were included: 279 couples with a carrier of a structural chromosomal abnormality and 428 non-carrier couples who served as controls. Univariable and multivariable logistic regression analyses, corrected for known risk factors for carrier status, were performed. The main outcome measure was the probability of carrier status.
RESULTS
Two hundred and fifty-six of 279 (92%) carrier couples and 381 of 428 (89%) non-carrier couples had experienced consecutive miscarriages (P = 0.21). A history of two or three consecutive miscarriages did not alter the probability of carrier status when compared with two [odds ratio (OR) 0.90, 95% confidence interval (CI) 0.48–1.7] or three (OR 0.71, 95% CI 0.39–1.3) non-consecutive miscarriages.
CONCLUSIONS
The sequence of preceding pregnancies is not a risk factor for carrier status. Therefore, couples with miscarriages interspersed with healthy child(ren) should be managed the same as couples with consecutive miscarriages regarding chromosome diagnosis.
A concern for new compounds in fertility treatment is the possible risk of perinatal complications or birth defects. To demonstrate long-term safety of ganirelix (GnRH antagonist) treatment in controlled ovarian stimulation (COS), follow-up data on pregnancy and neonatal outcome were analysed for 1000 fetuses (≥16 gestational weeks).
METHODS
Obstetrical and neonatal data on 839 pregnancies, resulting in 969 live born infants after ganirelix treatment were compared with a historical cohort of 753 pregnancies after long GnRH agonist (buserelin) treatment, resulting in 963 live born infants. All treatment cycles were performed in a single fertility centre. The infants were examined at the Universitair Ziekenhuis Brussel using an identical follow-up protocol. Incidence of major malformations (i.e. causing functional impairment or requiring surgical correction) was the primary end-point and was analysed by logistic regression including treatment, age of mother, IVF method and pregnancy type (singleton/multiple) as independent variables.
RESULTS
There were no relevant differences in maternal characteristics, fertilization method and pregnancy and delivery complications between the ganirelix and historical GnRH agonist groups. There were relatively more multiple pregnancies in the historical GnRH agonist group (31.9%) than the ganirelix group (18.7%; P < 0.0001). The groups were comparable with respect to pregnancy loss after 16 weeks gestation. The incidence of major congenital malformations in fetuses with gestational age ≥26 weeks was 5.0% in the ganirelix cohort versus 5.4% in the historical GnRH agonist group (odds ratio 0.94, 95% confidence interval, 0.62–1.42).
CONCLUSION
In terms of neonatal outcome and risk of major malformations, treatment with the GnRH antagonist ganirelix during COS is as safe as traditional GnRH agonists.
The aim of this study was to estimate whether or not the size of an endometrioma is related to the thickness of the ovarian parenchyma inadvertently excised along with the cyst wall.
METHODS
We performed a retrospective study including 35 women who had undergone endometrioma cystectomy, using an ovarian tissue sparing procedure. In total 38 specimens were studied by three pathologists as three women presented bilateral localizations, and all cyst diameters measured at least 30 mm. For each endometrioma, serial sections were performed, and on each section four different sites were randomly chosen to measure the thickness of glandular epithelium and stroma, of subjacent fibrosis, depending on the cyst, and of the ovarian parenchyma removed with the cyst. The diameter of the ovary was measured preoperatively either by MRI or ultrasound, and the area of the internal wall was then calculated. The relationships between the mean thickness of ovarian parenchyma removed and the variables were estimated and a multiple regression model identified independent predictors for ovarian parenchyma thickness.
RESULTS
Adjacent ovarian tissue was found in 37 cases (97%). The mean thickness of ovarian tissue removed was 1173 ± 711 µm and that of the cyst wall was 851 ± 499 µm. The thickness of the ovarian parenchyma removed presented a direct proportional relationship with cyst diameter (P = 0.015), and consequently with cyst wall area (P = 0.032). This relationship with cyst diameter was independent after adjustment on other variables (P = 0.032).
CONCLUSION
Endometrioma cystectomy even though performed with an accurate surgical technique leads to significant ovarian tissue removal, the thickness of which increases proportionally with cyst diameter.
Ovarian tissue (OT) cryopreservation and transplantation are options for fertility preservation in young female cancer patients.
METHODS
We investigated xenotransplantation of human OT into back muscle (B) of severe combined immunodeficiency mice. OT follicle content was evaluated by stereomicroscopy and pre-transplantation. Xenograft survival, follicular development (with/without FSH administration), apoptosis and vascularization were compared in B- versus K-site (under the kidney capsule) several times after grafting using histology, immunohistochemistry and magnetic resonance imaging. In vitro maturation (IVM) was also performed.
RESULTS
Anastomoses which developed from existing human and invading murine vessels were seen in OT at both sites, but angiogenesis was more prominent at the B- than K-site (P < 0.001). Vascularization and follicle size were correlated in the B-group (Spearman's coefficient 0.73; P < 0.001). FSH increased early (8 days) micro-vessel formation in B but not in K grafts (P < 0.0001, versus no FSH). B-site grafts showed a better histological morphology and survival (P = 0.0084), formation of larger antral follicles (P = 0.005), more metaphase-II (MII) oocytes, growing follicles (P = 0.028) and slightly fewer apoptotic follicles than K grafts. One MI oocyte from B underwent IVM and reached MII stage next day.
CONCLUSIONS
To our knowledge, this is the first report of MII and IVM–MII oocytes obtained from B xenografts. We report the largest oval-shaped antral follicles containing an MII oocyte obtained after OT xenotransplantation to date. Xenografting in the mouse B should be further explored as a method for human OT transplantation.
