Late follicular progesterone to estradiol ratio is not influenced by protocols or gonadotropins used.

OBJECTIVE: Increased progesterone level during follicular phase seemed to be associated with decreased pregnancy rate. STUDY DESIGN AND METHODS: A prospective cohort study, 1.1.2012 - 31.8.13. The Progesterone (P) and Progesterone/Estrogen (P/E2) level on ovulation induction day were compared between the protocols and the different gonadotropins used. Roc analysis was calculated to determine the cutoff of P/E2 to predict delivery rates. P/E2 ratio was calculated as PX1000/e2 level. MAIN RESULTS: One hundred thirty-nine patients were enrolled to the study. No difference in the P level at hCG stimulation day between different protocols, however, E2 and P/E2 ratio were significantly lower in the long protocol compare with antagonist protocol 1757.7 ± 923.2 vs. 1342.9 ± 1223; P = 0.003 and 0.48 ± 0.31 vs. 0.83 ± 0.87; P = 0.038). The endometrium was significantly thicker in the long group compare with short and antagonist. Significantly more top-quality embryos (TOP) were achieved in the antagonist group. Comparable results between the types of gonadotropins used in regards with cycle characteristics and pregnancy and delivery rates. The P/E2 ratio which can predict live birth rate was found to be 0.45, AUC = 0.632, p = 0.02 and 95 % CI 0.525-0.738 and a significantly higher pregnancy and delivery rates at a P/E2 bellow 0.45. CONCLUSION: Endometrial receptivity is determined by the complex interactions of E2 and P.

IVM results are comparable and may have advantages over standard IVF.

Retrieval of immature oocytes from unstimulated ovaries, followed by in vitro maturation (IVM) was originally proposed in order to avoid side effects of gonadotropin administration. The target is to eliminate or significantly reduce the risk of ovarian hyperstimulation syndrome (OHSS) in patients with polycystic ovary syndrome (PCOS), drug cost and burden on patients. This technology was also suggested in treatment of normo-ovulatory women, fertility preservation or infrequent conditions such as failure of oocytes to mature or repeated development of poor quality embryos. In this study we intended to examine the possibility that IVM results may be comparable to standard IVF. A PubMed database search from 1999-2013 was carried out for publications concerning the indications of IVM and study the possibility that IVM results may be comparable to standard IVF. In vitro maturation of the oocytes procedures obtained up to 35% clinical pregnancy rate in young women, comparable with in vitro fertilization (IVF) in many programs. The obstetric and perinatal outcomes of IVM cycles are comparable with IVF/ICSI cycles. In conclusion IVM may gradually replace IVF in certain cases, as the technique continues to develop and pregnancy rates continue to increase, being a promising and simple alternative approach to standard IVF in various indications.

In-vitro maturation of oocytes vs in-vitro fertilization with a gonadotropin-releasing hormone antagonist for women with polycystic ovarian syndrome: can superiority be defined?

OBJECTIVE: Patients with polycystic ovarian syndrome (PCOS) are at increased risk of ovarian hyperstimulation syndrome (OHSS) in controlled ovarian hyperstimulation cycles. Interventions to reduce the risk of OHSS in these patients include in-vitro fertilization (IVF) with a gonadotropin-releasing hormone (GnRH) antagonist, and retrieval of immature oocytes followed by in-vitro maturation (IVM). The aim of this study was to compare the outcomes of IVM and IVF-GnRH antagonist protocols in women with PCOS undergoing assisted reproductive technology. STUDY DESIGN: Retrospective cohort study. Records of women with PCOS who underwent IVM or IVF-GnRH antagonist protocols between 2010 and 2011 were reviewed. In total, there were 61 IVM cycles and 53 IVF-GnRH antagonist cycles. The treatment protocols were compared in terms of the number of oocytes retrieved, dose of gonadotropin administrated, fertilization rates, quality of embryos, pregnancy, and delivery and abortion rates. RESULTS: The number (mean±standard deviation) of mature oocytes did not differ significantly between the two groups (7.11±5.7 vs 8.16±5.07 for the GnRH antagonist group and the IVM group, respectively; p=0.38). The average dose of gonadotropin (1938 IU±838 IU/cycle vs 118±199 IU/cycle; p<0.001), fertilization rate (77% vs 60%; p<0.001) and high-quality embryo rate (58.8% vs 48.3; p<0.001) were significantly higher in the GnRH antagonist group compared with the IVM group. Pregnancy rates (40% vs 25%; p=0.08), livebirth rates per pregnancy (71% vs 53%; p=0.265) and abortion rates (10% vs 27%; p=0.17) were comparable. CONCLUSIONS: The IVM protocol can be an alternative for infertile women with PCOS who wish to prevent the potential adverse effects of gonadotropin treatment. Prospective studies are needed to compare the outcomes of these two treatment protocols.

Age and infertility: the clinical point of view.

With the demands of the modern western world of today, women delay the conception of their first child and this adversely impacts on their fertility. Vast attempts have been made to diagnose and counter ageing women infertility. In this literature review article, we bring forward theories which may account for the age-related decline of fertility and explained about the assessment and treatment modalities currently available. After concluding that ovarian stimulation with the use of gonadotrophins and clomiphene citrate is not useful in women of 40 year and over, it leaves us with in-vitro fertilization as the most suitable method of increasing the rate of successful pregnancies and live birth rates. It is important to campaign the effects age has on fertility since, even highly educated women, are not aware of the full impacts age has on fertility.

Multiple approaches for individualized fertility protective therapy in cancer patients.

In the last decade, fertility preservation has risen as a major field of interest, creating new interactions between oncologists and gynecologists. Various options, such as cryopreservation of ovarian tissue, have been developed and are currently routinely proposed in many centers. However, many of the options remain experimental and should be offered to patients only after adequate counseling. This paper addresses the efficiency and the potential of the different fertility preservation approaches.

Fertility preservation for cancer patients. Current options.

Prevalence of cancer has been increasing in the last years. Fortunately, during the last three decades, there has been a tremendous improvement in the success rates of cancer treatments and a continual rise in the survival rates. Given the improvement in survival rates with cancer treatment and developments in the field of reproductive medicine, fertility preservation for female cancer patients has become a very sensible issue. Today, several methods are available for preserving the reproductive potential of these patients. This review will focus on the options for fertility preservation offered to young cancer patients.

Mechanisms of follicle selection and development.

Follicle recruitment and selection, the process that gives rise to the dominant follicle (DF) and the physiological state of the DF are important areas of research. The selection of a single ovarian follicle for further differentiation and finally ovulation is a shared phenomenon in monovulatory species including humans. The DF is different from other follicles because it can escape atresia (the fate of all other follicles). The DF cells develop corpus luteum if exposed to the luteinizing hormone (LH) surge. Several mechanisms for DF selection have been proposed. Rising follicle stimulating hormone (FSH) concentrations induce the emergence of a follicle wave and cohort attrition occurs during declining FSH concentrations, resulting in DF selection. Cohort secretions are initially responsible for the decline in FSH, which is subsequently suppressed by the selected DF lowering it below the threshold of FSH requirements of all other cohort follicles. The DF acquires relative FSH-independence in order to continue growth and differentiation during further declining FSH concentrations. A transition from FSH- to LH-dependence is postulated as the mechanism for the continued development of the selected DF. In addition, FSH and insulin-like-growth factor (IGF) enhance each other's ability to stimulate follicle cell function. Access of IGF II to their receptors is regulated by IGF binding proteins that are in turn regulated by specific proteases; all of which have been ascribed a role in DF development. One other shared mechanism recently proposed for DF selection is the possible differential regulation of blood vessel formation. Anti-Müllerian hormone (AMH) also plays a critical role in selection of the DF. AMH levels decline as the size of the follicle increases. Once follicles reach a size at which they are dominant, it has largely disappeared. From the time a follicle has been selected, the follicle destined to ovulate greatly enlarges and shows marked changes in its steroidogenic activity. LH surge causes a significant decline in gap junctions leading to dissociation of mural granulosa cells (GC) and expansion of the cumulus-oocyte complex (COC). The oocyte resumes its meiosis and progresses from prophase 1 to metaphase 2 at the time of ovulation. The concept of DF selection could be applied to the in-vitro maturation (IVM) program. Understanding the mechanism of DF selection in menstrual cycles is the key to planning the optimal timing of oocyte retrieval in order to obtain competent oocytes and embryos. Although the timing of oocyte retrieval is still open to debate, there is evidence to suggest that it may be better to retrieve oocytes before the small cohort follicles complete the process of atresia following selection of the DF.

Placenta weight percentile curves for singleton and twins deliveries.

OBJECTIVE: To establish updated placental percentile nomograms in a large North American population for singleton and twin gestations for the use of researchers and clinicians. STUDY DESIGN: Data was extracted from our computerized registry; McGill Obstetrics and Neonatal Database (MOND). The registry includes all the obstetrical data on all deliveries at the McGill University, including placental weight, placental pathologies, maternal and perinatal complications. 20,635 singleton deliveries and 527 twin deliveries were included. Placental weight, gestational age at delivery, birth weight and gender were retrieved. Tables and figures for the 3rd,10th,25th, 50th, 75th 90th, and 97th percentile of placental weight by gestational age, placental weight by birth weight and placental to birth weight ratio by gestational age were produced. RESULTS: Tables and figures are presented for placental percentiles curves according to gestational age, gestational weight and gender for singleton and twin deliveries. In addition, tables and figures are presented for the ratio of placental weight to birth weight. CONCLUSIONS: Population percentile curves have been produced for placental weight and for the ratio of placental weight to birth weight to for singleton and twin deliveries.

Comparing the genetic changes detected in the primary and secondary tumor sites of ovarian cancer using comparative genomic hybridization.

Our objective was to compare the genetic abnormalities in the primary tumors of epithelial ovarian cancer and their associated secondary peritoneal implants using comparative genomic hybridization (CGH). CGH was performed on seven apparent stage III ovarian serous cancer cases. Dissected tissue samples from the primary tumor and from the metastatic peritoneal implant were obtained at initial surgical staging and analyzed in each case. We used CGH as this technique allows the entire genome of the tumor to be examined simultaneously for chromosomal imbalances without the need for tissue culture or targeting of specific loci. The chromosomal abnormalities detected in the distinct sites were then reviewed and compared. CGH studies were successful in all 14 samples from the seven patients. The analysis revealed chromosomal aberrations in six patients with certain repeated changes as amplification of 1q, 2p, 2q, 3q, 6q, 8q, and 12p and underrepresentation of 18q and X chromosomes. Comparing the genomes of the primary tumors with the metastatic samples showed four cases with a balanced metastatic CGH profile while the primary site was aberrant. Greater chromosomal complexity associated with the primary site was detected in two other patients. In one case, both primary and secondary sites had no detectable chromosomal imbalances. The cytogenetic patterns in six of the seven primary tumors showed complex karyotypic changes, unlike the inconsistent findings that were associated with the secondary sites. The chromosomes of the secondary sites expressed either normal genomes or fewer genetic aberrations. Such genomic heterogeneity between the primary and secondary sites may indicate that the secondary peritoneal implants are de novo carcinogenesis occurrences. The results may support the concept that at least part of advanced ovarian cancer is a multicentric disease in the early stages. Further genetic studies are needed to reassess this assumption.

Application of comparative genomic hybridization technique for detection of chromosomal aberrations in benign cystic teratoma.

Benign cystic teratoma, also known as dermoid cyst, is the most common of all ovarian neoplasms accounting for 10%-20% of all ovarian cysts. Most have a normal 46,XX karyotype. Less than 2% can undergo malignant transformation. By using the comparative genomic hybridization technique on nine benign ovarian cysts we were able to show two cases with chromosomal aberrations not seen before in dermoid cysts but known to be involved in malignant ovarian tumors. We speculate that these are the tumors carrying the potential for malignant transformation.