ESR1, ESR2 and FSH receptor gene polymorphisms in combination: a useful genetic tool for the prediction of poor responders.

PURPOSE: Previous studies in humans concluded that a multigenic model including specific FSHR, ESR1 and ESR2 genotype patterns may partially explain the poor response to FSH. The aim of our study is to analyse three different loci -polymorphisms in ESR1 Pvu II, ESR2 Rsa I and Ser680Asn FSH receptor gene- in a Greek population and their involvement in stimulation outcome and pregnancy rates. METHODS: Each locus was studied alone, and in combination with the others. We performed both restriction fragment length polymorphism analysis and real-time polymerase chain reaction. A total of 109 normally ovulating female patients underwent IVF or ICSI. RESULTS: Studying each locus alone, no significant results were drawn for ESR1 and ESR2 genes. Concerning the FSHR polymorphism, the women carrying the AA variant presented higher total amount of gonadotrophins used (P=0,048) and tended to have higher number of stimulation days (P=0,057). Considering the ESR1 and FSHR gene polymorphisms in combination, the TC/SA combination presents the highest number of pregnancies in poor responders group (3/4 pregnancies carried this genotype), in good responders group (4/12 pregnancies carried this genotype) and in the total population (10/26 pregnancies carried this genotype). Except the CC/AA combination, all other genotype combinations presented incidence of pregnancy, with TC/SA having the highest incidence. The CC/AA genotype presents the worst profile of ovulation induction, confirming a poor responder profile: the total amount of gonadotrophins used was highest in CC/AA group (P < 0,05). The peak E2, the number of follicles and of retrieved oocytes and the pregnancy rate were significantly lower (P < 0,05). This genotype combination seems to be over-presented in the poor responders group in a statistically significant way (P=0,038). Women with CC/AA combination have 1,5-2,4 times more risk to be poor responders in comparison with women that do not carry that combination. CONCLUSION: This study supports the hypothesis that a multigenic model, including the well studied ESR1 and FSHR genes is involved in the controlled ovarian stimulation outcome indicating that the CC/AA genotype presents the worst ovulation induction profile, while the TC/SA genotype presents the higher number of pregnancies in our population.

Autologous embryo-cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study.

In repeated implantation failure, the co-culture of human embryos with somatic cells has been reported to promote the improvement of embryos quality, implantation and pregnancy rate. It was reported that feeder cells can be more beneficial to the oocyte and embryo by detoxifying the culture medium and supporting embryo development via different pathways. In this study, 432 patients, each with a minimum of three repeated implantation failures, were accepted for a prospective randomized study with or without autologous cumulus cell embryo co-culture and transfer at day 3 or day 5-6. We also investigated the expression of leukaemia inhibitor factor (LIF) and platelet activating factor receptor (PAF-R) on day 3 confluent cumulus cells. The statistic analysis of the data showed significant difference of implantation and clinical pregnancy rates between classical culture and day 3 compared with co-culture and day 5-6 transfer. The molecular analysis showed that cumulus cells express the LIF and the PAF-R genes and confirmed the possible positive role of growth factors and cytokines in early embryo development. Embryo co-culture systems with autologous cells can be beneficial in routine in vitro fertilization for embryo selection and implantation improvement. More molecular investigations need to be done to improve elucidation of the complex dialogue between the embryo and feeder cells prior to implantation and to understand the involved biological function and molecular process during embryo development.

Natural cycle IVF and oocyte in-vitro maturation in polycystic ovary syndrome: a collaborative prospective study.

In-vitro maturation (IVM) was performed in 350 cycles for 262 unstimulated patients diagnosed with polycystic ovary syndrome who were primed with human chorionic gonadotrophin (HCG) before oocyte retrieval. In order to improve nuclear and cytoplasmic maturation, growth hormone was added to the maturation medium. Oocytes were recovered in 94.8% of the cycles, with a mean number of nine cumulus-oocyte complexes retrieved. Within 28 h, 62% of the oocytes reached the metaphase II (MII) stage, and 17.6% were MII after a further 20 h in culture. An ongoing pregnancy rate of 15.2% was obtained, but with a high miscarriage rate, 28% of the total with a positive betaHCG test assessed after embryo transfer. Cytogenetic and DNA fragmentation analysis of the embryos was not fundamentally different from what is classically observed in routine IVF. This observation implies that the results are not necessarily due to compromised oocyte quality after IVM, and that endometrial receptivity should also be considered, especially in IVM cycles where the follicular phase is dramatically shortened.

Pregnancy and assisted reproduction techniques in men and women after cancer treatment.

There are many male and female patients of young age diagnosed with some form of invasive cancer. With current treatment regimens, including aggressive chemotherapy, radiotherapy, bone marrow transplantation, and surgery, the cure rate for some malignancies now is very high. These treatments, however, can lead to gonadal failure and permanent infertility. Fertility preservation is a significant concern for such men and women faced with cancer treatment. Several alternatives have been attempted in an effort to preserve fertility in young women undergoing cancer treatment. Although ovarian tissue cryopreservation has recently been the focus of intense investigation, cryopreservation of embryos and mature oocytes has several advantages over ovarian tissue preservation. Also there are some strategies for minimizing female gonadal toxicity caused by cancer therapy including use of radiation shields, transposition of the ovaries out of the irradiation field, and suppression of ovaries by administration of gonadotropin releasing hormone agonists during adjuvant chemotherapy. In addition, fertility-saving surgical approaches are used in selected women with gynecologic cancers instead of more radical surgical procedures. Similarly, fertility preservation options such as conservative surgical approaches including partial orchiectomy with or without cryopreservation in testicular cancer patients and at least sperm cryopreservation in other male cancer patients should be offered before initiating therapy. Use of embryonic stem cells as a source of gametes also emerges as a hope in male and female cancer survivors.

Hydrosalpinx as an unusual complication of office hysteroscopy: case report.

Some complications of hysterocopy have been reported with increasing practice of the procedure both for diagnostic and operative procedures. However, complications associated with office hysteroscopy (HS) have not been well documented. A 35-year-old woman was accepted at our center for a second IVF cycle. She had had a history of primary infertility for nine years and no presumptive factors as a cause of infertility had been documented. Office hysteroscopy revealed a regular endocervix, endometrial cavity and bilateral internal tubal ostia. The patient was evaluated by pelvic examination (without any evidence of pelvic inflammatory disease) and transvaginal ultrasonograhy one month after the office HS for routine evaluation before the IVF cycle. There was an image compatible with left hydrosalpinx (6 mm in diameter) in her ultrasonographic examination that had not been detected before by the same physician using the same ultrasound equipment. Following an informative consultation with the patient, laparoscopy was performed and left hydrosalpinx was diagnosed. Salpingectomy was then carried out. The diagnosis of hydrosalpinx was confirmed by histological examination. To the best of our knowledge this is the first report of hydrosalpinx possibly caused by an office HS procedure.

Comparison of different gonadotrophin preparations in intrauterine insemination cycles for the treatment of unexplained infertility: a prospective, randomized study.

BACKGROUND: A comparison of the effectiveness of different gonadotrophin preparations in intrauterine insemination (IUI) cycles for patients with unexplained infertility was performed. METHODS: Two hundred and forty-one patients were prospectively randomized using computer-generated random numbers into three groups: 81 in the Follitropin alpha (Group I), 80 in the urinary FSH (uFSH) (Group II) and 80 in the hMG (Group III). The primary outcome was clinical pregnancy rate with duration of stimulation, total gonadotrophin dose, number of dominant follicles, clinical pregnancy rate, multiple pregnancy, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate being secondary outcomes. RESULTS: Clinical pregnancy rate was significantly higher in the rFSH group (25.9% in Follitropin alpha, 13.8% in uFSH and 12.5% in HMG groups; P = 0.04). There was no significant difference in terms of duration of stimulation, but mean FSH dose consumed per cycle was significantly lower in the recombinant FSH (rFSH) group compared with others (825 IU in Follitropin alpha, 1107 IU in uFSH and 1197 IU in HMG groups; P = 0.001). The number of follicles > or =16 mm diameter was significantly higher in the rFSH group compared with the uFSH and HMG groups (2.6 in Follitropin alpha, 1.3 in uFSH and 1.4 in HMG groups; P = 0.001). CONCLUSION: rFSH may result in a better outcome in IUI cycles for unexplained infertility.

Array comparative genomic hybridization profiling of first-trimester spontaneous abortions that fail to grow in vitro.

OBJECTIVES: Cytogenetic analysis of spontaneous abortion samples can be limited by culture failure. Failure to grow in vitro has traditionally been suspected to be due to in vivo death of tissue associated with spontaneous abortion (SAB) or simply technical factors of growth in culture. METHOD: We used array comparative genomic hybridization (array CGH) to investigate chromosomal imbalances in products of conception that failed to grow in vitro. RESULTS: Our data on 26 cases of SABs that failed to grow in culture are compared and contrasted with published data on cytogenetic findings following in vitro culture. The results revealed abnormalities uncommonly seen by classic cytogenetic methods. These abnormalities include high rates of double aneuploidy and autosomal monosomy. The data taken together suggest that classic cytogenetics of spontaneous abortion may yield normal karyotypes or selected abnormal karyotypes that permit cell proliferation in vitro while Array CGH detects other abnormalities. CONCLUSION: Array CGH is becoming an important clinical assay for unbalanced chromosome abnormalities whether cells grow in culture or not and in cases of analysis on one or few cells.

Pregnancy following intracytoplasmic sperm injection and preimplantation genetic diagnosis after the conservative management of endometrial cancer.

A rare case of a patient with conservatively treated endometrial carcinoma who conceived and delivered a healthy baby after the transfer of embryos with intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD) is presented. A 41-year-old woman had an office hysteroscopy in the infertility work-up and stage I endometrial adenocarcinoma was diagnosed. After conservative treatment, the patient underwent ICSI and PGD. She achieved pregnancy with two normal embryos. Two gestational sacs were observed but one of them was blighted. The patient subsequently delivered a healthy female infant. Repeated office hysteroscopy and endometrial sampling was performed after delivery. The appearance of the endometrium was normal on hysteroscopy, and the histology report was normal. The principal concern with medical therapy is that the lesion cannot be fully evaluated until the hysterectomy is performed, the nodes palpated, and the uterus is sectioned. The patient was referred to a gynaecological oncologist for definitive surgery.

An extraordinary case of four primary tumors in the same patient, involving the uterine cervix, lung, skin, and rectum.

Four primary cancers in one patient are fairly rare. Here we present a case of four primary tumors in such a patient. These cancers were cervical carcinoma and lung carcinoma, which occurred synchronously, and basal cell carcinoma of the skin and rectal carcinoma which occurred metachronously. A successful resection of two synchronous and two metachronous cancers, which has never previously been reported in this specific combination, is described.

Effects of hormone replacement on hemostasis in spontaneous menopause.

OBJECTIVE: To examine the effects of continuous combined estrogen-progesterone replacement therapy on coagulation and natural anticoagulant systems in spontaneous menopause. DESIGN: A randomized, double-blind, placebo-controlled study was conducted during a 6-month period to examine the effect of hormone replacement therapy (HRT) on blood coagulation parameters. One hundred-ten healthy postmenopausal women were randomized into two groups. Those in group 1 were given conjugated estrogen (0.625 mg/d, Premarin) and medroxyprogesterone acetate (5 mg/d, Farlutal), and those in group 2 were given identical tablets of placebo for 6 months. Serum levels of modified activated protein C resistance, antithrombin III, fibrinogen, factor VIIIa, factor VIII, factor IX, activated partial thromboplastin time, prothrombin time, thrombin time, and lipoprotein (a) were measured before and 6 months after the treatment and analyzed for changes in extrinsic and intrinsic coagulation parameters. RESULTS: At the end of the 6-month period, fibrinogen, lipoprotein (a), and activated protein C resistance levels were decreased significantly in the HRT group compared with the control group. Antithrombin III levels were increased, indicating antithrombin activity. Activated partial thromboplastin time, as a measure for intrinsic coagulation cascade, was prolonged in concert with decreased intrinsic coagulation factors, factor VIII, and factor IX (p < 0.05). In the extrinsic coagulation system, prothrombin time was significantly increased, although factor VIIa level was not changed (p > 0.05). CONCLUSION: Significant changes were observed in the coagulation parameters, which may further explain the cardioprotective effect of HRT.

Laparoscopic high lateral transposition of both ovaries before pelvic irradiation.

Lateral ovarian transposition before pelvic irradiation may preserve ovarian function in young women with gynecologic or nongynecologic cancer. We performed high lateral, transposition of both ovaries in a 17-year-old woman with primary non-Hodgkin lymphoma of the sacrum with subsequent preservation of menstrual cyclicity.

Women's perceptions of caesarean section: reflections from a Turkish teaching hospital.

Caesarean section as a contentious topic has attracted attention world-wide and different dimensions of the issue has been investigated. The primary reason behind these initiatives have been the upsurge of caesarean sections both in the developed and developing world and the realisation that the operation may not always contribute positively to the mother's and baby's health. By contrast, several studies have demonstrated both the short and long term negative effects. Research has also revealed that factors other than medical necessity play an important role in the decision to perform a caesarean section. Turkey, although reliable data does not exist, can be classified among the countries experiencing the caesarean epidemic, at least among highly educated and wealthy mothers. This research, exploring the perceptions of mothers in a teaching hospital with a high caesarean rate, is a rare example of its kind in Turkey. The main finding is the dissatisfaction of the mothers undergoing caesareans during their stay in the hospital.