In the follicular phase of the spontaneous menstrual cycle, only one follicle, out of a cohort of 10-20, usually completes maturation and ovulates to release a mature oocyte. The aim of ovarian stimulation in ART protocols is to overcome the selection of a dominant follicle and to allow the growth of a cohort of follicles, thus increasing the number of oocytes and hence embryos available, thereby increasing the chance of replacing, up to 3 viable embryos. However, a major challenge in ART programs is the treatment of patients in their mid 30's and over, as the chance of pregnancy and also live birth begins to dramatically decline. Preimplantation Genetic Screening studies over the last decade have identified that a major contributor to the reduction in embryo viability in older patients is the dramatic increase in the rate of eneuploidy. It has also been demonstrated that in women of advanced maternal age, the amount of mitochondrial DNA in the oocyte cytoplasm is significantly reduced. Additionally, some recent studies suggest that the ovarian stimulation regimen may also play an important role on improving embryo viability as tailoring ovarian stimulation with supplemental LH in the mid to late follicular phase may be beneficial to this older patient group. What could be the mechanisms by which LH supplementation may have an effect? In a recent study of Foong, et al. on low to poor respondrs to r-hFSH only stimulation, intra-follicular estradiol was significantly lower progesterone was significantly higher in poor to low responders to FSH. Previously, it has been demonstrated that in vitro, estradiol plays an important role in human oocyte cytoplasmic maturation manifesting itself im improved fertilization and cleavage rates. On the contrary, androstenedione can irreversibly block the effect of E2. Additionally in the ovine, E2 is assoiciated with upregulation of oocyte DNA repair enzymes. Studies carried out playing an aromatase inhibitor in the late stages of follicular development in the rhesus monkey, just prior to the period pf ovulation, showed reduced capacity on the oocyte to mature and a reduced rate of in vitro fertilization. Overall, it seems that LH may have a beneficial effect through a mechanism, which improves oocyte cytoplasmic maturation, either through E2 or some other intraovarian factor.
REPRODUCTIVE TECHNIQUES, ASSISTED

Polycystic ovary syndrome (PCOS) is characterized by oligo/anovulation, clinical or biochemical evidence of hyperandrogenism and polycystic ovaries, with exclusion of other related disorders. It affects 6 percent-10 percent of women of childbearing age and is the most common cause of anovulatory infertility. Insulin resistance and its compensatory hyperinsulinemia play a key pathogenic role in anovulation and infertility associated with PCOS. Evidence indicates that improving insulin resistance increases ovulation, the success of ovulation induction with clomiphene and pregnancy rates. Lifestyle modification, specifically a weight-reducing diet and exercise, is recommended as first-line therapy for all obese women with PCOS Clomiphene citrate is used as first-line therapy to induce ovulation in women with PCOS, followed by gonadotrophin administration for those who failed to respond to clomiphene. A novel therapeutic approach has emerged from the observation that most women with PCOS suffer from hyperinsulinemic insulin resistance and from evidence that strongly suggests that the elevated circulating insulin concentration impedes ovulation. Insulin sensitizing agents (ISA) used for ovulation induction in PCOS are metformin, rosiglitazone, pioglitazone, troglitazone and d-chiro inositol. The last two are not available. Use of rosiglitazone and pioglitazone (Category B drugs) for PCOS have been reported. Their primary mechanism of action is to enhance peripheral insulin sensitivity. Metformin (Category B drug) has been used in most studies on PCOS. Metformins primary mechanism of action is to reduce hepatic glucose production by improving hepatic insulin sensitivity. It is a safe, effective and rational treatment for the metabolic and endocrine abnormalities in PCOS. Kim, et al. recommended institution of ISA only after clomiphene failure induction. ISA are useful in the treatment of obese and non-obese women with PCOS. In a multinational, randomized, single-blind placebo controlled trial, metformin monotherapy yielded a higher rate of ovulation compared to placebo but a head-to-head trial of ISA vs. clomiphene for initial ovulation induction has not been reported. However, substantial evidence exists, including results from randomized clinical trials, that metformin enhances the likelihood of successful ovulation induction with clomiphene. A multicenter, randomized, double-blind, placebo-controlled trial showed a 75 percent ovulation rate with clomiphene-metformin vs. 27 percent in the clomiphene-placebo group. Fifty eight percent conceived in the clomiphene-metformin group vs. 13 percent in the clomiphene-placebo group Metformin treatment may allow a reduced rate of hyperstimulation with FSH therapy and may reduce the risk of multiple gestation. No randomized, double-blind, placebo-controlled trial of ISA as an adjuvant to gonadotrophin ovulation inductionhas been reported In an abstract at the 1999 meeting of the ASRM, it was reported that metformin increased the number of mature oocytes retrieved from women with PCOS undergoing gonadotrophin-stimulated IVF-ET and ICSI. Women with PCOS have a 30 percent-50 percent first trimester pregnancy loss and 36 percent-82 percent of women with recurrent pregnancy loss are reported to have PCOS. Hyperinsulinemia maybe the important factor in the pregnancy losses. A recent pilot study and a preliminary report both reported a 10 fold reduction in miscarriage in women with PCOS treated throughout pregnancy with metformin. No prospective controlled trials have addressed this issue. In PCOS, use of metformin is associated with a 10-fold reduction in gestational diabetes (31 percent to 3 percent). It also reduces insulin resistance and insulin secretion, thus decreasing the secretory demands imposed on pancreatic beta cells by insulin resistance and pregnancy. It is not teratogenic.
POLYCYSTIC OVARY SYNDROME

There are relatively few effective clinical options for preserving female fertility, particularly following aggressive chemotherapy and or radiotherapy treatment protocols. This paper reviews the scientific background, current technology, clinical results and potential future applications of two methods of preserving female fertility-ovarian tissue cryopreservation and oocyte cryopreservation. These technologies are investigational, although rapidly evolving and their list of appropriate indications may be expanded in the future.
CRYOPRESERVATION ; FERTILITY AGENTS, FEMALE

In Vitro Fertilization (IVF) is an established treatment approach for infertility based on the developments the past quarter century. However, there are still a number of reasons which prevent both doctors and patients from embarking on this available treatment option. The current indication for IVF (including endometriosis, tubal pathology, anovulation, male factor infertility-and unexplained infertility) are reviewed considering prognosis for pregnancy using IVF as compared to no/more conventional treatment. Evidence-based data are presented. Also, maternal age as a factor for success in IVF treatment is reviewed. Local setting situations which contribute to delays in treatment are also tackled.
FERTILIZATION IN VITRO

In considering the uptake of ART around the world and in particular regions, it is crucial to consider outcome and what is considered to be successful treatment. Standardisation of reporting for comparability between clinics and countries is essential. This will be affected by multiple pregnancy and efforts to minimize them and the anxiety relating to possible problems such as imprinting abnormalities. General access is influenced by ethical by ethical and religious value systems, which in turn impinge on the political nature of discussions about provision. Of primary importance is the extent of access to treatment; the need for ART in the first instance is related to the prevalence of STDs and the quality of reproductive health services in the community. Access is critically determined by whether ART is provided by the public health system, otherwise it is the preserve of the better off. However, the public health system does not usually accord ART high priority. Even in the UK where there has been a positive analysis of the evidence base by the public health service, funding remains a major issue. ART is not explicitly included in the UN Millennium Development Goals, however they could be interpreted as including it. Of importance was the WHO Ministerial Summit on Health Research held in Mexico last November. Its recommendations and timetable were aimed at overcoming health system constraints to the delivery of all health care, in particular promoting access in low income settings. Successful implementation of any recommendations will likely have a long term impact on the provision of all health care. Perhaps 50% of all infertility can be treated by ART. It should no longer be seen as the high tech end of provision, only required by a few. It should be widely available and included in public health provision. The technical challenge is to reduce the cost and increase the efficacy. But the greater challenge for the medical scientific communities is to educate the public and the politicians to understand the techniques and their implications. Cost-benefit analyses will be required to demonstrate appropriate and wise spending and to show a rational case for the public health expenditure. The development of trusted regulatory system will also be necessary, ideally with legal flexibility to encompass scientific advances. Only then can public health provision of ART be envisaged; funding allocation must follow for it to become readily available. Although ART births are now contributing significantly to national data in some countries, the social impact on the world community will continue to be minimal until these changes have taken place.
REPRODUCTIVE TECHNIQUES, ASSISTED

Unlike the GnRH agonists, which have been routinely used in ovarian stimulation protocols for almost 20 years, the GnRH-antagonist acts via a dose-dependent competetive blockade of the pituitary GnRH receptors. This results in an immediate suppression of gonadotrophin secretion (in particular LH) from the anterior pituitary. Despite the new advantages of this new class of substances, the controversial discussion about the influence of the antagonist of the implantation and embryo quality has been ongoing for the last few years. New data from recent meta analysis have demonstrated that the clinical pregnancy rate per cycle is equivalent between antagonist protocols, however there is a sugnificant reduction in the amount of FSH used and the incidence of OHSS. Recently, flexible protocols where the GnRH antagonist is applied according to leading follicle size rather than a fixed of stimulation have been developed in order to prevent a premature LH surge. A recent meta-analysis of four randomised trials comparing fixed vs flexible starting day for the GnRH antagonist concluded there was no statistically significant difference in pregnancy rates, but a significant reduction in the amount of FSH utilized in favour of the flexible protocol. A series of studies have however raised concern about late administration of the GnRH antagonist, as used in a flexible protocol. In the three studies, the implantation and pregnancy rates were higher when the antagonist was initiated on a fixed day (stimulation day 6) compared to administration in a flexible protocol according to follicle size (-15mm). Whilst Kolibianakis, et al. reported no difference in overall pregnancy rate in flexible over fixed day antagonist administration, the implantation rate was lower in the flexible protocol, when there were no follicles of -15mm on the stimulation day 6. In this group, higher concentrations of LH and oestradiol were observed to antagonist administration. In a second study, Kolibianakis, et al reported that profound suppression of LH after GnRH antagonist suppression was associated with a significantly higher ongoing pregnancy rate. They argued that exposure of the genital tract/oocyte to LH may adversely affect the implantation rate, mainly by altering endometrial receptivity. One issue here that ma have complicated the interpretation of the results is the very late administration of the GnRH antagonist (-15mm). It is generally recommended that the antagonist should administered when the leading follicle is 14mm at he very latest. Co-treatment with oral contraceptive pill (OCP) programming can also be utilized with GnRH antagonists in order to facilitate scheduling the start of FSH therapy, rather than waiting for the patient to have spontaneous menses. There are now a number of studies reporting the use of OCP pill programming with either daily 0.25mg or single dose 3mg Cetrotide in routine ART and also poor responder patients. Future studies in this area are needed to elucidate the optimal preparation protocol in GnRH antagonist cycles. However, the data that are emerging seem to support that previous cycle preparation can make a clinical contribution to the outcome of the antagonist treatment cycle.
GONADOTROPIN-RELEASING HORMONE ; OVULATION INDUCTION

To study the profile of menopausal women, particularly age, reproductive history body mass index, abdominal circumference, smoking history, duration of menopause in years, type and duration of use of hormone replacement therapy, calcium intake, frequency of exercise, history of fracture and their bone mineral density.
Human ; Female ; Aged 80 and over ; Aged ; Middle Aged ; Adult ; OSTEOPOROSIS ; WOMEN ; ;

Estrogen replacement therapy (ERT) is known to significantly decrease menopausal health risks, thus, a survey of 200 women attending a tertiary hospital was conducted. Assess their attitudes toward menopause and ERT to determine factors that might increase its use revealed that women taking their ERT were more likely to know that decreased estrogen hormone causes osteoporosis. All groups however believed that natural approaches to menopause are more preferable and ERT should be reserved for women with distressing symptoms. The study suggests that a systematic educational approach could increase awareness and use of ERT especially if the recommended therapy will not cause vaginal bleeding and will cost minimally.
Human ; MENOPAUSE ; ESTROGEN REPLACEMENT THERAPY

A case of successful twin pregnancy following severe ovarian hyperstimulation syndrome (OHSS) is reported. Ignorance of this complication of ovulation induction may result to serious morbidities, and even mortality. With awareness of this condition, preventive measures can be instituted. Similarly, early recognition and prompt treatment may result to a reduction in the rate of its progression to a severe, potentially fatal stage. Consequently, a favorable outcome may be achieved.
Human ; Female ; Adult ; OVARIAN HYPERSTIMULATION SYNDROME ; PREGNANCY, MULTIPLE

Objective: To determine which of the following factors at initial surgery-such as diameter of largest endometriotic cyst, number of cysts, diseases severity, type of surgery (laparoscopy versus laparotomy), or postoperative medical therapy-best correlated with the time of recurrence of ovarian endometrioma. Design: A retrospective descriptive study was performed on 25 patients who underwent initial surgical excision of endometriotic cyst and had cyst recurrence demonstrated either on ultrasound or repeat surgery. The clinical presentation of cyst recurrence was described. The operative findings of the first and second surgeries were compared. Factors which may affect the time of cyst recurrence were evaluated. Results: Cyst recurrence was demonstrated by ultrasound in 24 (96 percent) cases; repeat surgery for recurrence was done in only 10 (40 percent) cases. The different factors in the initial surgery: type of operation, size, number, and laterality of the endometriotic cyst, disease severity, adhesions and postoperative medical therapy, did not influence the time of recurrence of ovarian endometrioma. Disease severity was a significant factor on repeat surgery. Conclusion: The different factors aforementioned, which were present in the first surgery, did not influence the time of recurrence of ovarian endometrioma.
Human ; Female ; Adult ; ENDOMETRIOSIS ; RECURRENCE