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Follicle stimulating hormone levels on cycle day 3 predict ovulation stimulation response.

AIM: To determine the value of basal follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on cycle day 3 in predicting the ovulation stimulation response in patients receiving exogenous gonadotropins for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). METHODS: One hundred eleven consecutive females with infertility due to various etiologies were investigated. Cycle day 3 serum levels of FSH, LH, and E2 were determined prior to ovulation induction with a combination of clomiphene citrate and human gonadotropins. Follicular growth was monitored ultrasonically, and when appropriate, oocytes were recruited, counted, graded, and then used, as prearranged, for either IVF or GIFT. Basal hormone levels were compared to the peak E2 concentration, the number of follicles aspirated, and the number of preovulatory oocytes recovered following drug therapy. Details of resulting pregnancies were also recorded. RESULTS: Patients with low basal FSH levels (< 11.5 mIu/ml) yielded a higher mean number of preovulatory oocytes than those with high values (> 11.5 mIu/ml), i.e., 6.7 oocytes per cycle vs 2.5 oocytes (P < 0.001). In the low group 97% of cycles yielded more than three fertilizable oocytes compared to 42% in the high group (P < 0.5). There were 16 term pregnancies (16%) in the low group and 1 (8.3%) in the high group. Basal LH and E2 levels did not improve on the ability to distinguish between different populations of infertile females who responded differently to ovulation induction. CONCLUSION: Cycle day 3 FSH levels are predictive of the ovulation response and probability of pregnancy in stimulated cycles and can be of value in patient selection and counseling in IVF and GIFT programs.

Abortion, Spontaneous↗

Induction of single ovulation by sequential follicle-stimulating hormone and pulsatile gonadotropin-releasing hormone treatment.

OBJECTIVE: To induce single follicular ovulation by sequential treatment with FSH and pulsatile GnRH. DESIGN: Prospective study. PATIENTS: Eighteen hypogonadotropic anovulatory patients. INTERVENTIONS: In sequential treatment, daily FSH injection was switched to pulsatile GnRH administration (20 micrograms/120 minutes SC) when the follicle diameter reached 11 mm. In conventional FSH treatment, daily FSH injection was continued. In both cycles, hCG was given when the diameter of the dominant follicle reached 18 mm. MAIN OUTCOME MEASURES: Developed follicle numbers and serum FSH concentrations during treatment. RESULTS: Single follicular development was achieved in 80.0% of cycles by sequential treatment but in no cycle by conventional FSH treatment. The number of developed follicles was 1.26 +/- 0.55 (mean +/- SD) on sequential treatment and 3.94 +/- 1.48 on conventional FSH treatment. Preovulatory FSH level was significantly lower on sequential treatment than on conventional FSH treatment (5.26 +/- 1.80 versus 11.55 +/- 3.43 mIU/mL [conversion factor to SI unit, 1.00]). CONCLUSION: The sequential treatment achieved single follicular development without complications. The sequential FSH-pulsatile GnRH treatment may offer a better chance for development of a single dominant follicle and ovulation.

Adult↗

Further observations of the ovarian response of the tammar wallaby (Macropus eugenii) to exogenous gonadotrophins: an improved method for superovulation using FSH/LH.

This study reports the development of an improved superovulation protocol in the monovulatory tammar wallaby, Macropus eugenii. Treatment with pregnant mare's serum gonadotrophin (PMSG; 10-20 IU) inhibited follicle development in the corpus luteum (CL)-bearing ovary and only 2-3 eggs per female could be recovered after ovulation induction with gonadotrophin releasing hormone (GnRH; 3 x 30 microg at 3-h intervals) or porcine luteinizing hormone (LH; 4, 5 or 8 mg) 3 days after PMSG priming. Treatment with porcine FSH (8 x 6 mg at 12-h intervals for four consecutive days) was found to override this inhibition and resulted in the recovery of 7-13 eggs per female after ovulation induction with porcine LH (4 mg on day 5). For these animals, there was no difference in numbers of developing follicles, ovulation sites and eggs recovered between the CL- and non-CL-bearing ovaries. This FSH/LH protocol was effective in both cycling and non-cycling females, and multiple ovulation occurred from about 36 h after LH treatment. After LH treatment, eggs were recovered from the oviduct at 36-50 h. At 51-57 h, 12-25% of eggs were recovered from the uterus, and by 75 h all eggs were recovered from the uterus. It is concluded that the described FSH/LH protocol used results in higher ovulation success than the PMSG/GnRH method.

Animals↗

Results of gonadotrophin stimulation with the option to convert cycles to in vitro fertilization in cases of multifollicular development.

BACKGROUND: To avoid a high cancellation rate and/or a high multiple pregnancy rate due to multifollicular development in gonadotrophin stimulated cycles, such cycles were converted in the same cycle to in vitro fertilization/embryo transfer (IVF/ET). The results from a four year period using this strategy are summarized. PATIENTS AND METHODS: Seventy-three anovulatory women (seven WHO group I, 66 WHO group II) were studied during this period. In a majority of the cycles a GnRH-analogue was used for down-regulation according to a long protocol, followed by stimulation with FSH and/or hMG. RESULTS: Out of 154 WHO group II gonadotrophin stimulation cycles intended for ovulation induction, 25 cycles were converted to IVF. The pregnancy and delivery rates in the IVF-converted cycles were 50% and 41%, respectively, and 31% and 22% when gonadotrophin stimulation was followed by intercourse. The cancellation rate, including both ovulation induction and IVF cycles, was 15% and the multiple pregnancy rate was 30%, mainly twins. Lean women achieved better outcome than obese women. In WHO group I only 12 cycles were performed. One cycle was converted to IVF resulting in delivery and one cycle was cancelled. The pregnancy- and delivery rates were both 50% when gonadotrophin stimulation was followed by intercourse. CONCLUSION: It is concluded that the option to convert a gonadotrophin stimulation cycle to IVF in the same cycle, in cases of multifollicular development, seemed to be a good alternative. The conversion results in a low cancellation rate and a low incidence of high order multiple pregnancies. Patients should be informed of this opportunity before entering ovulation stimulation.

Adult↗

A preliminary study on the induction of dioestrous ovulation in the mare--a possible method for inducing prolonged luteal phase.

BACKGROUND: Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares. METHODS: In this preliminary study, in an attempt to induce ovulation during the luteal phase, human chorionic gonadotropin (hCG) (3000 IU) was injected intramuscularly in four mares (experimental group) in the luteal phase when a dioestrous follicle > or = 30 mm was detected. A fifth mare included in this group was not treated due to no detectable dioestrous follicles > or = 30 mm. Four control mares were similarly injected with saline. The mares were followed with ultrasound for 72 hours post injection or until ovulation. Blood samples for progesterone analysis were obtained twice weekly for one month and thereafter once weekly for another two to four months. RESULTS: Three of the hCG-treated mares ovulated within 72 hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days respectively. One treated mare never ovulated after the hCG injection and progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone levels in the control mares were below 3 nmol/l within nine days after saline injection, except for one mare, which developed a spontaneously prolonged luteal phase of 72 days. CONCLUSION: HCG treatment may be a method to induce prolonged luteal phases in the mare provided there is a dioestrous follicle > or = 30 mm that ovulates post-treatment. However, the method needs to be tested on a larger number of mares to be able to draw conclusions regarding its effectiveness.

Animals↗

Effect of traditional herbal medicine on serum testosterone levels and its induction of regular ovulation in hyperandrogenic and oligomenorrheic women (author's transl).

Eight infertile hyperandrogenic and oligomenorrheic women were investigated for lowering serum testosterone levels and inducing regular ovulation by Shakuyaku-Kanzo-To (mixed extracts of Paeonae Radix and Glycyrrhizae Radix). Serum testosterone levels (50-160 ng/dl) were lowered to less than 50 ng/dl in 7 patients by Shakuyaku-Kanzo-To 5-10 g daily administered for 2-8 weeks. Six of 7 patients ovulated regularly and 2 of 6 patients conceived. Serum LH levels, which were shown to be above 30 mIU/ml in 7 patients were lowered to less than 30 mIU/ml in 5 patients by dexamethasone 1 mg daily administered for 6.5 days. All of these patients ovulated regularly by Shakuyaku-Kanzo-To. No side effects were observed. Thus, Shakuyaku-Kanzo-To is indicated for lowering serum testosterone levels and inducing regular ovulation and pregnancy in infertile hyperandrogenic patients, especially in the patients whose serum LH levels were shown to be lowered to less than 30 mIU/ml by dexamethasone.

Adult↗

Higher-order multiple pregnancy associated with metformin in women with polycystic ovary syndrome: two cases and review of the literature.

OBJECTIVE: To describe the first reported cases of two women with polycystic ovary syndrome (PCOS) desirous of pregnancy who conceived trichorionic pregnancies following ovulation induction with metformin alone and metformin plus clomiphene. DESIGN: Case report. SETTING: Private fertility practice. PATIENT(S): Two women with polycystic ovary syndrome, one lean and one overweight, both oligoovulatory and not undertaking their first cycle of treatment. INTERVENTION(S): Ovulation induction by metformin alone or in combination with clomiphene MAIN OUTCOME MEASURE(S): Higher-order multiple pregnancy (triplet or greater). RESULT(S): Two cases of trichorionic pregnancy. CONCLUSION(S): This is the first report of higher-order multiple pregnancies resulting from the use of either metformin alone or in combination with clomiphene. The additive effects of adjunctive treatments such as weight reduction, ovarian drilling, and clomiphene and metformin therapy may result in an increased incidence of higher-order multiple pregnancy and women need to be counseled about this risk. Further research is required to quantify the risk of this event per treatment cycle.

Adult↗

[Ovarian hyperstimulation syndrome].

The ovarian hyperstimulation syndrome (OHSS) is caused iatrogenically by the application of agents for ovulation induction. The syndrome may be characterized by different symptoms sometimes including an increase in blood viscosity, changes in coagulation parameters as well as renal perfusion. Although the incidence of the severe forms of the syndrome is very low, there is a general increase due to the wide spread use of ovulation induction. The only treatment of the syndrome is prevention by close monitoring of serum oestradiol levels and follicular development.

Ascites↗

Prognostic significance of endometrial evaluation by ultrasonography in ovulation induced cycles.

OBJECTIVE: To find out prognostic significance of pre-ovulatory endometrial evaluation by ultrasound scanning after exposure to the drugs during different protocols of ovulation induction with particular reference to clomiphene citrate and to correlate with pregnancy rate. METHODS: The thickness and texture of endometrium were the two biophysical parameters considered to be evaluated by ultrasonography. The cycles of 47 women of primary infertility were studied after ovulation induction by 4 types of protocols with or without clomiphene citrate. RESULTS: The pregnancy rate was recorded highest (36%, 5/14) in the exclusive treatment group of clomiphene citrate protocol. Most of the women in this group suffered with low level (<6 mm) endometrial thickness, but all five women who showed A-grade endometrium became pregnant. The exclusive human menopausal gonadotrophin treated group and sequential protocol group achieved low pregnancy rates as 22% (2/9) and 27% (3,11). The luteinizing hormone releasing hormone analogue and follicle stimulating hormone protocol achieved 31% (4/13) pregnancy rate with more number of women showing A-grade endometrium quality. CONCLUSION: The quality of endometrial texture rather than thickness of endometrium, can be considered as one of the strong prognostic factors to predict pregnancy rate in a majority of women.

Adult↗

Ovarian cancer in infertility patients.

The possibility that ovulation induction increases the risk of ovarian cancer remains unproven. However, recent studies suggest that both infertility and endometriosis may be independent risk factors. Despite the various case reports and epidemiological studies performed the association between the use of infertility drugs and ovarian cancer remains weak. The fact that the women who were the first to use ovulation agents are now reaching mid-life means that future studies should show whether any association exists. Hence, there is a need now for large prospective trials to be performed to establish whether an association between ovulation induction agents and ovarian cancer truly exists.

Adult↗

Gonadotropin-releasing hormone agonist and human menopausal gonadotropin (hMG) short protocol, but not hMG alone, rescues the corpus luteum from the preceding cycle.

OBJECTIVE: To determine whether ovulation induction regimens, particularly the short protocol, has an effect on the corpus luteum (CL) from the previous cycle. DESIGN: Infertility patients were followed in an academic research environment. Patients were treated with either the short protocol (GnRH agonist [GnRH-a] and hMG) or hMG alone in a controlled ovarian hyperstimulation cycle. SETTING: Infertility center in academic setting. PATIENTS: Patients requiring ovulation induction. INTERVENTIONS: The blood samples were drawn on day 2 or 3 as a baseline before initiation of any treatments, generally on day 5 and usually every other day thereafter until ovulation. Serum P, E2, and relaxin were determined. MAIN OUTCOME MEASURES: Serum P, E2 and relaxin. RESULTS: Patients receiving hMG alone showed no change in serum P levels in the first few days of treatment whereas most short-protocol patients (18/30; 60%) showed an increase of P within 3 days of the initiation of treatment. The increase in P almost always was associated with an increase in relaxin as a marker of the luteal production of this P. CONCLUSION: The short protocol with its flare of gonadotropins is able to stimulate the CL from the previous cycle, resulting in an early increase in P that comes from the CL as indicated by its association with an increased relaxin in the same subjects.

Corpus Luteum↗

Clinical management of functional ovarian cysts: a prospective and randomized study.

Most ovarian cysts in women of reproductive age are physiological (functional) and patients have been treated for years with oral contraceptives to obtain the resolution of these cysts. Expectant management has been suggested to have the same effectiveness as hormonal treatment but such suggestions come from studies including all kinds of cysts. The objective of the present study was to assess the resolution of functional ovarian cysts, observed after ovulation induction, with expectant management and hormonal treatment and also to determine the period of time necessary for the resolution of the cysts. For this purpose, 53 patients with ovarian cysts, observed by transvaginal ultrasound within the first 5 days of a cycle after ovulation induction, were randomized to have expectant management (group A) or to receive oral contraception (group B) for one cycle. If the cyst persisted, the patient was followed for another cycle, without any treatment. Within the 50 women who completed the trial, a complete resolution of the cysts was observed in 19/25 (76%) and 18/25 (72%) in groups A and B respectively. On the other hand, all the persistent cysts disappeared after a second cycle without any treatment. In conclusion, expectant management is as effective as oral contraceptives for the resolution of functional ovarian cysts induced by ovarian stimulation. However, studies with a larger number of cases are needed to increase the power of the results and to obtain a firm conclusion.

Adult↗

Severe ovarian hyperstimulation syndrome despite low plasma oestrogen concentrations in a hypogonadotrophic, hypogonadal patient.

Ovarian hyperstimulation syndrome (OHSS) is the most serious, life-threatening, iatrogenic complication of ovulation induction. The importance of excessive oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration as a predictor and factor in the pathophysiology of OHSS has been extensively studied and discussed. We present the case report of a woman with hypogonadotrophic hypogonadism who developed severe OHSS during ovulation induction with urinary human follicle stimulating hormone (FSH) and HCG in the presence of low circulating oestradiol concentrations. The implication of FSH treatment and complications in hypogonadotrophic hypogonadal patients, and the role of preovulatory oestradiol concentrations in the prediction of OHSS, are discussed.

Adult↗

Infertility: a review of 291 infertile couples over eight years.

Two hundred and ninety-one infertile couples were studied over an 8-year period. Anovulation was the most common cause of infertility, being the causative factor in half of the patients. Ovulation induction with clomiphene or cyclic hormone therapy readily achieved pregnancy in the majority of these patients. The distribution of other etiologic factors was fairly uniform, but treatment was much less successful. Thorough evaluation of both partners is advised both for treatment purposes and as a more accurate guide to the prognosis for conception. Furthermore, even in the presence of oligospermia, ovulation induction may be successful in achieving a pregnancy.

Anovulation↗