Surgery: Laparoscopic unwinding of adnexal torsion caused by ovarian hyperstimulation

A case of laparoscopic unwinding of a twisted enlarged ovaryand Fallopian tube caused by ovarian hyperstimulation is presented.The laparoscopic unwinding was simple and was carried out ina short time. The patient's post-operative course was uneventful.Complications such as thromboembolism were not observed andthe post-operative ovarian function was well preserved aftersuch procedures. Preservation of the ovary is highly importantin young infertile women. Prompt diagnosis with an immediateunwinding of the twisted adnexa by a laparoscopic techniquecan produce a valuable outcome     

Laparoscopic therapy of an intact primary ovarian pregnancy with ovarian hyperstimulation syndrome: case report

A case of an intact primary ovarian pregnancy with ultrasonographic demonstration of heart motion following ovarian stimulation is presented. After preoperative ultrasonographic confirmation of an extrauterine pregnancy, proof of the ovarian localization was achieved by intra-operative ultrasonographic visualization during a diagnostic laparoscopy on post-menstrual day 48. A moderate ovarian hyperstimulation syndrome with a concomitant increase in size, vulnerability and vascularity of the ovaries presented an additional challenge for the surgical approach. However, thanks to the early diagnosis of the ectopic pregnancy localization, a laparoscopic organ-preserving removal of the intact ovarian pregnancy was successfully performed. In this way, the fertility of the patient, who had previously undergone contralateral ovariectomy, was preserved. To our knowledge, this represents the first such treatment to be reported in the medical literature. Improvements in diagnosis and therapy of ovarian pregnancy are reviewed.     

Basal and day 12 inhibin concentrations in the prediction of ovarian response to gonadotrophins in women with PCOS

BACKGROUND: In this study, we aimed to investigate whether basal and day 12 serum total inhibin concentrations in women with polycystic ovarian syndrome (PCOS) were of predictive value for the estimation of the ovarian response to gonadotrophins. METHODS: Ovulation induction with a very low dose gonadotrophin protocol, starting with 37.5 IU/day, was performed for 40 cycles on 35 patients with PCOS. Day 3 (basal) serum total inhibin, FSH and oestradiol concentrations; day 12 dominant follicle diameter, inhibin and oestradiol concentrations and midluteal serum progesterone concentrations were measured during the 40 cycles. The correlations between basal and day 12 inhibin concentrations and some critical ovulation monitoring parameters were investigated. RESULTS: Ovulation was obtained in 14 out of 40 cycles: 21% of cycles with basal inhibin <1.0 IU/ml; 33.3% of cycles with basal inhibin between 1.0-1.9 IU/ml; and 83.3% of those with inhibin concentrations > or =2 IU/ml were ovulatory (P < 0.05). Ovulation was achieved in 91.6% of the cycles with a day 12 inhibin concentration > or =4 IU/ml. CONCLUSIONS: Basal inhibin concentrations may determine poor and good responders to ovulation induction with very low dose gonadotrophin protocol in patients with PCOS. The day 12 inhibin concentration was found to be a more sensitive parameter than the oestradiol concentration in the prediction of follicular maturation.     

Endocrinology: Ovarian response in consecutive cycles of ovarian stimulation in normally ovulating women

Ovarian stimulation combined with intra-uterine insemination(IUI) is an effective treatment of non-tubal infertility butmost women undergo several cycles of treatment to achieve apregnancy. This prospective study was designed to assess theconsistency (or variation) of ovarian responses and the effectof various ovarian stimulation protocols on this consistencyin consecutive cycles of ovarian stimulation and IUI in womenwith non-ovulatory infertility. A total of 86 regularly menstruatingovulating patients each completed three to six cycles of ovarianstimulation and IUI (n = 347 cycles). Ovarian stimulation wasachieved by sequential clomiphene citrate/human menopausal gonadotrophin(HMG), HMG-only or combined gonadotrophin-releasing hormoneanalogue—HMG protocols in 33, 29 and 24 patients respectively,and each patient used the same protocol consistently throughoutthe study. Standard methods were used to monitor ovarian responseand to perform IUI. Using each patient as her own control, repeatedmeasurements analysis of variance revealed consistency of ovarianresponse in consecutive ovarian stimulation cycles, as shownby the number and mean diameter of maturing pre-ovulatory follicles,peak plasma oestradiol, duration of stimulation and mean HMGrequirements. This consistency existed using any of the ovarianstimulation protocols. We conclude that regularly menstruatingand ovulating women are likely to have similar ovarian responsesin consecutive cycles of ovarian stimulation and IUI if thesame ovarian stimulation protocol is used consistently. Thisis expected to reduce the frequency of treatment monitoringand clinic visits and to help schedule the timing of IUI.     

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.     

Isolated recurrent torsion of the Fallopian tube: case report

We report a rare clinical case of recurrent isolated torsion of the Fallopian tube. An 18 year old woman presented with acute right lower quadrant pain, nausea and vomiting. Torsion of the Fallopian tube was detected by laparoscopy and detorsion was performed. Two years later, a second similar episode of pelvic pain recurred. Having in mind the first episode, diagnosis was facilitated and detorsion was performed in accordance with the patient's wishes. However, the dilemma of ideal management of recurrent cases of torsion of the same tube remains open for discussion. The possibility of torsion of the Fallopian tube and recurrent torsion of the tube, although rare, should be considered in any patient with acute onset of lower abdominal pain.     

Recurrent cholestasis following ovarian hyperstimulation syndrome: case report.

This is a case report illustrating a patient who developed recurrent cholestasis during a twin pregnancy following in-vitro fertilization (IVF) treatment. On the first occasion cholestasis developed unusually in the first trimester, and on the second occasion, it presented in the way that obstetric cholestasis (OC) is commonly seen in the third trimester.     

Ovarian torsion: a complication of GIFT. A report on two cases and literature review.

Two cases of ovarian torsion after gamete intra-Fallopian transfer are described and the roles of ovarian manipulation during the procedure, ovarian hyperstimulation and pregnancy as predisposing factors are discussed. The relevant literature is reviewed.     

Chronic ovarian torsion after vaginal hysterectomy: a case with metastatic serous ovarian cancer

Ovarian torsion refers to partial or complete rotation of the ovary on its ligamentous support, often resulting in partial or complete obstruction of its blood supply. It is one of the most common gynecologic surgical emergencies and may affect females of all ages, but it is relatively rare in postmenopausal women. Chronic adnexal torsion with complete occlusion of the ovarian blood supply results in necrosis and loss of ovarian function. Clinical symptoms and signs are not specific and definitive diagnosis is often challenging. In this case report, we present a 65-year-old woman with chronic ovarian torsion that was detected 7 years after vaginal hysterectomy. Approximately 3% of postmenopausal cases with adnexal torsion are associated with malignancy. Ovarian torsion incidence is low in postmenopausal ovarian cancer due to the progression of accompanying inflammation, which causes immobility of the ovarian mass.     

Subclavian vein thrombosis following IVF and ovarian hyperstimulation: a case report

Thromboembolic phenomena are a serious consequence of assisted reproductive technology. We present a case of upper extremity deep vein thrombosis (DVT) at 7 weeks gestation following ovarian hyperstimulation syndrome (OHSS) and IVF. Three weeks after recovering from OHSS, the patient presented with left neck pain and swelling. Ultrasound revealed a thrombus in the left jugular vein and left subclavian vein. Low molecular weight heparin (LMWH) was initiated with symptom resolution within 1 week. The patient remained on LWMH throughout her pregnancy and delivered at term. A literature review showed 97 published cases of thromboembolism following ovulation induction. A majority of these cases was associated with OHSS and pregnancy and the site of involvement was predominantly in the upper extremity and neck. Infertility physicians and obstetricians should be aware of this complication and keep in mind that it may occur weeks after resolution of OHSS symptoms.     

Relationship between the threshold of ovarian sensitivity to human menopausal gonadotrophin stimulation and in-vitro fertilization treatment outcome

In a retrospective study of 813 oocyte retrieval–embryotransfer cycles in women with normal follicle stimulating hormoneand luteinizing hormone concentrations, we sought to investigatethe relationship between the amount of human menopausal gonadotrophin(HMG) used for ovarian stimulation and treatment outcome. Patientswere divided into three groups: group A patients (495 cycles)required <40 ampoules of HMG and had a predicted probabilityfor pregnancy of 25% per embryo transfer; group B patients (165cycles) required 41–77 ampoules per cycle, with a predictedprobability rate for pregnancy of 5–25% per embryo transfer;and group C patients (153 cycles) required >77 ampoules ofHMG and the predicted probability for pregnancy was <5% perembryo transfer. Groups C and A differed significantly (P <0.005). The mean oestradiol concentration on the day of HCGadministration in group C was 6412 pmol/l, and the mean numberof eggs retrieved was seven. The highest success rates werefound when up to 2.5 ampoules of HMG were required for eachegg or 4.4 ampoules for each embryo. The lowest rates were obtainedwhen >4.8 ampoules of HMG were necessary for each oocyteor >9.6 ampoules for each embryo (P < 0.005). We identifieda group of infertile patients who required excessive amountsof HMG to achieve a fair degree of steroidogenesis, number ofeggs and number of embryos but who had very low pregnancy rates.Although all other relevant parameters were normal, this mayhighlight the beginning of ovarian–gamete insufficiencybefore the basic hormonal status is affected. In cases of repeatedfailure, oocyte donation should be considered.     

Endocrinology: Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation

The aim of the present study was to investigate whether reducingthe amount of luteinizing hormone (LH) in gonadotrophic preparationsimpairs follicular growth in in-vitro fertilization (IVF) cyclesduring suppression of endogenous LH levels. A selected groupof 20 IVF patients was randomly divided into two groups. Onegroup was treated with Org 31338 [follicle stimulating hormone(FSH)/LH 3: 1], the other group with Metrodin® (purifiedFSH), both during pituitary down-regulation with buserelin.A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrationsof FSH, LH, oestradiol and progesterone were determined frequentlyand serial ultrasound examinations were performed. Multiplefollicular growth with concomitant rise of oestradiol levelswas observed in all cycles. The duration of the stimulationphase was shorter in the group treated with Org 31338 than inthe group treated with Metrodin. The number of follicles andoocytes and the fertilization rate was larger and the mean embryoquality was higher in the Org 31338 group, but the differencesdid not reach statistical significance. No significant differenceswere found in hormonal values. In women with normal endocrineprofiles, lowering of the LH activity in gonadotrophic preparationsduring gonadotrophin-releasing hormone agonist treatment resultsin adequate ovarian stimulation. However, a preparation withsome LH needed a shorter stimulation than a purified FSH preparation.Whether the other beneficial effects of Org 31338 also occurin a larger population needs further investigation.     

An aggressive philosophy in controlled ovarian stimulation cycles increases pregnancy rates

To assess the effect of timing of human chorionic gonadotrophin(HCG) administration in ovarian stimulation cycles, the serumoestradiol concentration and follicle profile were comparedwith the clinical pregnancy rate in 582 ovarian stimulation— intra-uterine insemination (OS—IUI) cycles and3917 in-vitro fertilization—embryo transfer (IVF—ET)cycles. The pregnancy rates increased exponentially with increasingoestradiol in both OS—IUI and IVF—ET cycles (R²= 0.720, P < 0.001) but then decreased in OS-IUI cycles whenthe oestradiol concentration exceeded 5000 pmol/l (R² = 0.936,P < 0.004) at HCG administration. In OS—IUI cyclesthe percentage of cycles with three or more mature follicles( 18 mm diameter) increased up to an oestradiol concentrationof 5000 pmol/l then declined, mirroring the pregnancy rate (R²= 0.900, P = 0.01). The exponential increase in pregnancy ratewith increasing oestradiol concentration in IVF—ET cyclessuggests that high oestradiol concentration does not have adeleterious effect on endometrial receptivity. The decreasein pregnancy rate in OS-IUI cycles when oestradiol concentrationexceeded 5000 pmol/l reflected fewer mature follicles, resultingfrom premature administration of HCG to avoid severe ovarianhyperstimulation syndrome (OHSS). We recommend that HCG administrationbe delayed until multiple follicles have reached maturity, andreducing the risk of severe OHSS by converting high risk OS—IUIcycles to IVF—ET, or if funds or facilities are unavailable,transvaginally draining all but four or five mature follicles.     

Allograft of ovarian cortex between two genetically non-identical sisters: case report

Aggressive chemotherapy and radiotherapy generally result inthe loss of both endocrine and reproductive functions. In 1990,a woman aged 20 years, presenting with -thalassemia major, underwentchemotherapy (busulfan and cyclophosphamide) and total bodyirradiation (TBI) before bone marrow transplantation (BMT),the donor being her 17-year-old HLA-compatible sister. The treatmentresulted in premature ovarian failure. In 2006, after excisionof ovarian cortical fragments from the HLA-compatible sister,these fragments were immediately sutured to the ovarian medullaof the patient. Both procedures were performed by laparoscopy.Six months after reimplantation, vaginal ultrasonography andhormone concentrations indicated recovery of ovarian secretionand function. From 6 to 11 months, the patient experienced menstrualbleeding and the development of a follicle concomitant withhigh estradiol levels. Eleven months after reimplantation, twofollicles were detected and punctured under vaginal ultrasonographiccontrol. Two mature oocytes were retrieved and inseminated byICSI. Two embryos (2- and 3-cell) were obtained. Allotransplantationof fresh ovarian tissue was laparoscopically performed betweentwo genetically non-identical sisters. Restoration of ovarianfunction was achieved after six months. Oocyte retrieval andembryo development were demonstrated.     

Immunology: Pregnancy and birth in an in-vitro fertilization cycle after controlled ovarian stimulation in a woman with a history of allergic reaction to human menopausal gonadotrophin

We report a case of an allergic reaction to i.m. injectionsof urinary human menopausal gonadotrophin (HMG) and a successfulmanagement of the problem by using recombinant follicle stimulatinghormone (rFSH) administered i.m. The patient underwent two zygoteintra-Fallopian transfer (ZIFT) cydes, in which ovarian stimulationwas carried out by a combination of gonadotrophin-releasinghormone agonist (GnRHa) and HMG. A twin pregnancy was achievedafter the first cycle. The patient delivered two premature boysat 28 weeks one of whom died after 25 days from severe respiratorydistress. During the second ZIFT cycle the patient developedan allergic reaction with redness and swelling in many partsof her body 30 min after every HMG injection. Despite the allergicreaction, the cycle was completed with a second ZIFT. No pregnancywas achieved in this cycle. The patient came back to our centrefor a third attempt during which ovarian stimulation was accomplishedwith a combination of GnRHa and rFSH. Adverse reaction as wellas general discomfort were not reported by the patient duringovarian stimulation with rFSH. A successful singleton pregnancywas achieved after intrauterine embryo transfer with the birthof a healthy girl after 38 weeks. If any allergic reaction ispresent after injection of HMG it is advisable to stimulatea subsequent cycle with rFSH.     

Endocrinology: Serum concentrations of dimeric inhibin during the spontaneous human menstrual cycle and after treatment with exogenous gonadotrophin

A recently described two-site enzyme immunoassay incorporatinga pre-assay oxidation step was validated and used to measureserum concentrations of dimeric inhibin in five normally cyclingwomen and in 13 women undergoing gonadotrophin therapy. Recombinanthuman inhibin A (standard) gave an assay response curve whichwas parallel to those for human serum samples and recovery ofexogenous inhibin added to serum samples before assay was quantittive(109±8%, n=11). During the normal menstrual cycle dimericinhibin concentration increased from 9.0±2.0 pg/ml duringthe early follicular phase to reach a mid-cycle peak of 55.3±11.1pg/ml coincident with the pre-ovulatory gonadotrophin surge.After falling to 27.9 ± 5.7 pg/ml 1 day after the luteinizinghormone surge, inhibin then rose in parallel with serum progesteroneto reach a peak value of 115.6 ± 19.3 pg/ml during themid-luteal phase, before falling to 14.1±4.9 pg/ml bythe onset of next menses. During the follicular phase, dimericinhibin concentrations were closely correlated with those ofserum oestradiol (r,= 0.69; P< 0.001), whereas during theluteal phase they were most closely correlated with serum progesteroneconcentrations (r = 0.73; P < 0.001). Daily treatment withhuman meno-pausal gonadotrophin promoted a progressive increasein serum dimeric inhibin concentration which increased 20-foldin 6 days. In the same period total-inhibin (measured by radioimmunoassay)increased 5-fold, while serum oestradiol increased 30-fold.Although the assay cross-reacted with dimeric inhibin formsof molecular masses in the range 200–30 kDa, chromatographyof superovulatory human serum revealed that the fully processed 30 kDa form is the predominant circulating form, although aproportion of this (30%) is reversibly associated with serumbinding protein(s).     

An unusual steroid-producing ovarian tumour: case report

The rapid onset of virilization in a post-menopausal woman is usually the result of androgen secretion from a tumour of adrenal or ovarian origin. Androgen secreting neoplasms of the ovary are rare and usually show autonomous secretion. Rarely, these may be driven by the high levels of gonadotrophins seen in the post-menopausal state. We describe the case of a 67-year-old woman with high serum testosterone and estradiol in association with the high gonadotrophin levels usually associated with the post-menopausal state. All hormonal parameters showed a significant suppression over 12 h with administration of the GnRH antagonist, cetrorelix. This observation implies that excess hormone synthesis was of ovarian origin and was gonadotrophin driven. Localization of the tumour was not possible by conventional ultrasound or computerized tomography scanning, but was achieved by venous sampling. Complete cure was achieved by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with restoration of the endocrine profile to that expected for a post-menopausal woman. Rapidly acting GnRH antagonists, such as cetrorelix, offer a safe and useful diagnostic and therapeutic option in the management of ovarian steroid-secreting tumours, which show gonadotrophin dependency.     

Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series

In patients with poor response to ovarian stimulation with gonadotrophins, growth hormone (GH) is sometimes used to increase paracrine insulin-like growth factor-1 (IGF-1) effect. We postulated that dehydroepiandrosterone (DHEA) administration to poor responders would augment gonado-trophin effect via a similar mechanism. Baseline ovarian stimulation response to a cycle with DHEA in five healthy non-smoking women <41 years old was compared with day 3 FSH <20 mIU/ml. All had documented poor response to vigorous gonadotrophin administration. After day 2 ultrasounds, DHEA-sulphate (DHEA-S), FSH, human chorionic gonadotrophin (HCG), and testosterone were measured, and the women were given 80 mg/day of oral micronized DHEA for 2 months. While still on DHEA, they underwent ovarian stimulation with FSH given i.m. twice a day, and HCG (10 000 IU) at follicular maturity, followed by intrauterine insemination. Cycle parameters assessed were peak oestradiol, and peak oestradiol/ampoule. The DHEA/ovarian stimulation cycles occurred between 4 and 24 months after the control cycles. After 2 months DHEA treatment, DHEA-S increased to 544 +/- 55 microg/dl, and testosterone increased to 67.3 +/- 6.1 ng/dl. All five subjects (six cycles; one subject had two DHEA cycles) had increased responsiveness; peak oestradiol concentrations increased from 266.3 +/- 69.4 pg/ml to 939.8 +/- 418.9 pg/ml. The oestradiol/ampoule ratio increased in all six cycles, by a mean of 2.94 +/- 0.50 fold (P = 0.012). One of the cycles resulted in a delivered twin pregnancy. In this small series, DHEA improved response to ovarian stimulation even after controlling for gonadotrophin dose. Supplemental DHEA treatment during ovarian stimulation may represent a novel way to maximize ovarian response.     

Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility

BACKGROUND: Adding clomiphene citrate (CC) to FSH for controlled ovarian stimulation (COS) decreases FSH dose required for optimum stimulation. However, because of its anti-estrogenic effects, CC may be associated with lower pregnancy rates offsetting the FSH-dose reduction benefit. Previously, we reported the success of aromatase inhibition in inducing ovulation without antiestrogenic effects. METHODS: A prospective pilot study that included women with unexplained infertility undergoing COS and intrauterine insemination. Thirty-six women received the aromatase inhibitor letrozole + FSH, 18 women received CC + FSH and 56 women received FSH only. Each woman received one treatment regimen in one treatment cycle. All patients were given recombinant or highly purified FSH (50-150 IU/day) starting on day 3 to 7 until day of hCG. RESULTS: The FSH dose needed was significantly lower in letrozole + FSH and CC + FSH groups compared with FSH-only without a difference in number of follicles >1.8 cm. Pregnancy rate was 19.1% in the letrozole + FSH group, 10.5% in the CC + FSH group and 18.7% in the FSH-only group. Both pregnancy rate and endometrial thickness were significantly lower in CC + FSH group compared with the other two groups. Estradiol (E2) levels were significantly lower in the letrozole + FSH group compared with the other two groups. CONCLUSIONS: Similar to CC, aromatase inhibition with letrozole reduces FSH dose required for COS without the undesirable antiestrogenic effects sometimes seen with CC.     

Prediction of severe ovarian hyperstimulation syndrome by free serum vascular endothelial growth factor concentration on the day of human chorionic gonadotrophin administration.

In this prospective study the concentration of circulating vascular endothelial growth factor (VEGF) was followed in 10 patients with severe ovarian hyperstimulation syndrome (OHSS) after ovarian stimulation and in 15 patients without OHSS. VEGF was assayed by means of two different commercially available kits as either free or total VEGF in serum. The concentration of free VEGF was significantly higher on the days of human chorionic gonadotrophin (HCG) administration (309.4 +/- 165.0 versus 190.3 +/- 127.8 pg/ml, P < 0.05) and embryo transfer (315.0 +/- 125.2 versus 209.3 +/- 137. 2 pg/ml, P < 0.05) in the OHSS compared to the control group. No such difference existed with respect to total circulating VEGF. In addition, there was no significant rise in the free or in the total serum VEGF concentration in the OHSS patients or the controls from the day of HCG administration up to the days of oocyte retrieval or embryo transfer. A cut-off concentration of 200 pg/ml free serum VEGF concentration on the day of HCG treatment resulted in a sensitivity of 90% and a specificity of 80% for the prediction of OHSS development. This is the first report on the parallel measurement of free and total VEGF in serum following ovarian stimulation. The value of the proposed cut-off concentration should be confirmed in a study of a larger group of women.