Petra De Sutter

Perinatal outcome of pregnancies after assisted reproduction: A case-control study

PURPOSE A matched case-control study of all pregnancies obtained after either IVF or ICSI was conducted to investigate the perinatal outcome. METHODS Three hundred eleven singleton and 115 twin pregnancies obtained after assisted reproduction were studied. Controls were selected from a regional register and were matched for maternal age, parity, singleton or twin pregnancy, and date of delivery. RESULTS No significant difference was observed for gestational age at delivery, birth weight, incidence of congenital anomalies, and incidence of perinatal mortality between ART (singleton and twin) pregnancies and spontaneous controls. ART twin pregnancies showed a higher incidence of preterm deliveries than control pregnancies (52 vs 42%; P < 0.05) and needed more neonatal intensive care (47 vs 26%; P < 0.05). CONCLUSIONS From this case-control study it is concluded that the perinatal outcome of ART singleton pregnancies is not different from that in matched controls. ART twin pregnancies showed a higher incidence of preterm deliveries than control pregnancies and needed more neonatal intensive care.

Long-term Assessment of the Physical, Mental, and Sexual Health among Transsexual Women

INTRODUCTION Transsexualism is the most extreme form of gender identity disorder and most transsexuals eventually pursue sex reassignment surgery (SRS). In transsexual women, this comprises removal of the male reproductive organs, creation of a neovagina and clitoris, and often implantation of breast prostheses. Studies have shown good sexual satisfaction after transition. However, long-term follow-up data on physical, mental and sexual functioning are lacking. AIM To gather information on physical, mental, and sexual well-being, health-promoting behavior and satisfaction with gender-related body features of transsexual women who had undergone SRS. METHODS Fifty transsexual women who had undergone SRS >or=6 months earlier were recruited. MAIN OUTCOME MEASURES Self-reported physical and mental health using the Dutch version of the Short-Form-36 (SF-36) Health Survey; sexual functioning using the Dutch version of the Female Sexual Function Index (FSFI). Satisfaction with gender-related bodily features as well as with perceived female appearance; importance of sex, relationship quality, necessity and advisability of gynecological exams, as well as health concerns and feelings of regret concerning transition were scored. RESULTS Compared with reference populations, transsexual women scored good on physical and mental level (SF-36). Gender-related bodily features were shown to be of high value. Appreciation of their appearance as perceived by others, as well as their own satisfaction with their self-image as women obtained a good score (8 and 9, respectively). However, sexual functioning as assessed through FSFI was suboptimal when compared with biological women, especially the sublevels concerning arousal, lubrication, and pain. Superior scores concerning sexual function were obtained in those transsexual women who were in a relationship and in heterosexuals. CONCLUSIONS Transsexual women function well on a physical, emotional, psychological and social level. With respect to sexuality, they suffer from specific difficulties, especially concerning arousal, lubrication, and pain.

Reproductive wish in transsexual men

BACKGROUND Hormonal therapy and sex reassignment surgery (SRS) in transsexual persons lead to an irreversible loss of their reproductive potential. The current and future technologies could create the possibility for female-to-male transsexual persons (transsexual men) to have genetically related children. However, little is known about this topic. The aim of this study is to provide information on the reproductive wishes of transsexual men after SRS. METHODS A self-constructed questionnaire was presented to 50 transsexual men in a single-center study. RESULTS The majority (64%) of transsexual men were currently involved in a relationship. Eleven participants (22.0%) reported having children. For eight participants, their female partner was inseminated with donor sperm, whereas three participants gave birth before hormonal therapy and SRS. At the time of interview, more than half of the participants desired to have children (54%). There were 18 participants (37.5%) who reported that they had considered freezing their germ cells, if this technique would have been available previously. Participants without children at the time of investigation expressed this desire more often than participants with children (χ²; test: P= 0.006). CONCLUSIONS Our data reveal that the majority of transsexual men desire to have children. Therefore, more attention should be paid to this topic during the diagnostic phase of transition and to the consequences for genetic parenthood after starting sex reassignment therapy.

Efficiency of assisted oocyte activation as a solution for failed intracytoplasmic sperm injection

Failed fertilization after intracytoplasmic sperm injection (ICSI) can occur due to an oocyte activation defect. In these cases assisted oocyte activation (AOA) may help but efficiency is still unknown. Prior to AOA, the mouse oocyte activation test (MOAT) can be carried out by injecting human spermatozoa into mouse oocytes to evaluate their activating capacity. According to the MOAT activation percentage achieved, patients were classified into three groups: 0-20% (16 patients); 20-85% (seven patients); 85-100% (seven patients). For AOA, CaCl(2) was injected together with spermatozoa followed by a double Ca(2+) ionophore treatment. The fertilization rates before application of AOA in 50 cycles were 6%, 22% and 14% in, respectively, groups 1, 2 and 3 without any pregnancy. Fertilization and pregnancy rates after AOA in 61 cycles were significantly increased to 75% and 34% for group 1, 73% and 43% for group 2, and 75% and 17% for group 3 (P < 0.0001 and P < 0.004, respectively). Application of AOA results in normal fertilization and pregnancy rates in patients whose spermatozoa show deficient activation. When MOAT reveals no activation deficiency in spermatozoa, AOA still allows for high fertilization and acceptable pregnancy rates. The obstetric and neonatal outcomes after AOA were normal as no malformations were observed.

Tracking the progression of the human inner cell mass during embryonic stem cell derivation

The different pluripotent states of mouse embryonic stem cells (ESCs) in vitro have been shown to correspond to stages of mouse embryonic development. For human cells, little is known about the events that precede the generation of ESCs or whether they correlate with in vivo developmental stages. Here we investigate the cellular and molecular changes that occur during the transition from the human inner cell mass (ICM) to ESCs in vitro. We demonstrate that human ESCs originate from a post-ICM intermediate (PICMI), a transient epiblast-like structure that has undergone X-inactivation in female cells and is both necessary and sufficient for ESC derivation. The PICMI is the result of progressive and defined ICM organization in vitro and has a distinct state of cell signaling. The PICMI can be cryopreserved without compromising ESC derivation capacity. As a closer progenitor of ESCs than the ICM, the PICMI provides insight into the pluripotent state of human stem cells.

A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility

BACKGROUND Male factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLCζ). Previously, we identified a point mutation in an infertile male resulting in the substitution of histidine for proline at position 398 of the protein sequence (PLCζ(H398P)), leading to abnormal PLCζ function and infertility. METHODS AND RESULTS Here, using a combination of direct-sequencing and mini-sequencing of the PLCζ gene from the patient and his family, we report the identification of a second PLCζ mutation in the same patient resulting in a histidine to leucine substitution at position 233 (PLCζ(H233L)), which is predicted to disrupt local protein interactions in a manner similar to PLCζ(H398P) and was shown to exhibit abnormal calcium oscillatory ability following predictive 3D modelling and cRNA injection in mouse oocytes respectively. We show that PLCζ(H233L) and PLCζ(H398P) exist on distinct parental chromosomes, the former inherited from the patients mother and the latter from his father. Neither mutation was detected utilizing custom-made single-nucleotide polymorphism assays in 100 fertile males and females, or 8 infertile males with characterized oocyte activation deficiency. CONCLUSIONS Collectively, our findings provide further evidence regarding the importance of PLCζ at oocyte activation and forms of male infertility where this is deficient. Additionally, we show that the inheritance patterns underlying male infertility are more complex than previously thought and may involve maternal mechanisms.

Risks associated with bacterial vaginosis in infertility patients: a systematic review and meta-analysis

STUDY QUESTION Is bacterial vaginosis (BV) associated with the cause of infertility and does BV impinge on conception rates and early pregnancy loss following IVF? SUMMARY ANSWER The incidence of BV is significantly higher among patients with tubal infertility when compared with patients with non-tubal infertility. BV does not impinge on conception rates but is significantly associated with preclinical pregnancy loss, though not with first trimester abortion. WHAT IS KNOWN ALREADY BV is prevalent in patients with infertility, as evident from studies across the world. STUDY DESIGN, SIZE, DURATION This study is a meta-analysis of data on the prevalence of BV in women with infertility, the association between BV and the cause of infertility, and the associations between BV and conception rates and early pregnancy loss following IVF. The meta-analyses of the various topics involved different numbers of studies: prevalence of BV with infertility--12 studies, association with tubal infertility--3 studies and associations with conception rates--6 studies, with early preclinical pregnancy loss--2 studies and with clinical pregnancy loss--4 studies. PARTICIPANTS/MATERIALS, SETTING, METHODS Systematic literature searches of the electronic databases, PubMed, EMBASE, CINAHL, the Cochrane Library and ISI Web of Knowledge were performed up to September 2012. Studies were included if they reported on, at least, one of the following: prevalence of BV in infertility patients, association between BV and the cause of infertility, association between BV and conception rates with IVF or association between BV and early pregnancy loss. Studies were considered eligible if BV was diagnosed through standardized criteria like Nugents criteria or Hay-Isons criteria. In none of the studies, infertility as such was defined, but patients were described as unselected patients undergoing IVF. MAIN RESULTS AND THE ROLE OF CHANCE The estimated prevalence of BV (Nugent score >6) in infertile women is 19% [95% confidence interval (CI): 14-25%]. Abnormal microflora including BV and intermediate microflora (Nugent scores 4-10) occurs in 39% of the infertile patients (95% CI: 26-52%). BV is significantly more prevalent in women with infertility compared with antenatal women in the same population [OR (odds ratio) 3.32, 95% CI 1.53-7.20]. BV is significantly more prevalent in women with tubal infertility compared with women with other causes of infertility (OR 2.77, 95% CI 1.62-4.75). BV is not associated with decreased conception rates (OR 1.03, 95% CI 0.79-1.33). Similarly, none of the studies found an association between abnormal vaginal flora and conception rates following IVF treatment. BV is associated with a significantly elevated risk of preclinical pregnancy loss (OR 2.36, 95% CI: 1.24-4.51). BV is not associated with an increased risk of first trimester miscarriage (OR 1.20, 95%CI: 0.53-2.75). LIMITATIONS, REASONS FOR CAUTION All included studies were centre based. In addition, publication bias cannot be ruled out. Furthermore, all estimates are obtained using an absolute minimum of studies. The standard error on the estimates is so large that it does not allow for any formal statistical conclusions regarding heterogeneity between the effects reported in different studies. WIDER IMPLICATIONS OF THE FINDINGS It needs to be recognized that most inferences drawn in our study rely on a limited number of studies, potentially, endangering the generalizability of our findings. Moreover, all studies on cause of infertility in relation to BV included had a cross-sectional design and, therefore, do not allow for causal inferences. Still, there is strong circumstantial evidence that supports a causal link between BV and tubal infertility. Studies with a longitudinal design, on the other hand, strongly support a relation between BV and early pregnancy loss. Unfortunately, no study looked beyond first trimester fetal loss, although it is plausible that the high preterm birth rates with IVF are, at least, in part attributable to BV.

Prevention of severe ovarian hyperstimulation by coasting

OBJECTIVE To evaluate the efficiency of withholding gonadotropins and deferring the administration of hCG until E2 levels start dropping (coasting) in the prevention of ovarian hyperstimulation syndrome (OHSS) in a high-risk population. DESIGN Retrospective case-control study. SETTING In vitro fertilization program at a university center. PATIENT(S) The case group consisted of 120 women undergoing ovarian stimulation for IVF who were considered to be at risk for ovarian hyperstimulation (serum E2 levels >2,500 pg/mL or >20 follicles at the time of hCG administration). INTERVENTION(S) Gonadotropin administration was withheld when serum E2 levels exceeded 2,500 pg/mL, and hCG administration was delayed until E2 levels dropped below 2,500 pg/mL. Outcomes were compared with those from 120 matched patients in whom serum E2 levels and the number of follicles at the time of hCG administration were comparable to those at the beginning of coasting (control group). MAIN OUTCOME MEASURE(S) Incidence of moderate and severe OHSS. The number of oocytes retrieved and pregnancy rate (PR) were compared in both groups. RESULT(S) Coasting decreased the incidence of moderate and severe OHSS. The odds ratio of severe OHSS in the coasting group was 0.11 (95% confidence interval 0.01-0.86). Although the number of oocytes was significantly lower in the coasting group (19.7 +/- 0.6 versus 22.1 +/- 0.6), coasting did not affect the PR (37.5% versus 36.7%). CONCLUSION(S) Our study indicates that coasting is an efficient method for reducing the incidence and severity of OHSS without compromising the PR.

Assisted oocyte activation following ICSI fertilization failure

The capacity of intracytoplasmic sperm injection (ICSI) to permit almost any type of spermatozoa to fertilize oocytes has made it the most successful treatment for male factor infertility. Despite its high success rates, fertilization failure following ICSI still occurs in 1-3% of couples. Assisted oocyte activation (AOA) is being increasingly applied in human assisted reproduction to restore fertilization and pregnancy rates in couples with a history of ICSI fertilization failure. However, controversy still exists mainly because the artificial activating agents do not mimic precisely the initial physiological processes of mammalian oocyte activation, which has led to safety concerns. This review addresses the mechanism of human oocyte activation and the relatively rare phenomenon of fertilization failure after ICSI. Next, it describes the current diagnostic approaches and focuses on the application, efficiency and safety of AOA in human assisted reproduction.

Ovarian response to recombinant human follicle-stimulating hormone: a randomized, antimüllerian hormone–stratified, dose–response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection

OBJECTIVE To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrations. DESIGN Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-<2.1 ng/mL]; high: 15.0-44.9 pmol/L [2.1-6.3 ng/mL]) trial. SETTING Seven infertility centers in four countries. PATIENT(S) Two hundred sixty-five women aged ≤37 years. INTERVENTION(S) Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle. MAIN OUTCOME MEASURE(S) Number of oocytes retrieved. RESULT(S) The number of oocytes retrieved increased in an rhFSH dose-dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2-0.7) and 1.0 (95% confidence interval 0.7-1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum. CONCLUSION(S) Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level. CLINICAL TRIAL REGISTRATION NUMBER NCT01426386.