Neri Laufer

Micro-organ ovarian transplantation enables pregnancy: a case report

A 19-year-old thalassemic woman had tissue from one of her ovaries cryopreserved prior to bone marrow transplantation, total body irradiation and sterilizing chemotherapy. As expected, premature ovarian failure resulted from this treatment. Transplantation of her thawed ovarian tissue resulted in return of menstrual cycling and the patient then underwent several IVF cycles. The patient, however, had poor ovarian response to hyperstimulation. We thus considered an alternative approach based on the observation that very thin ovarian fragments that preserve the basic ovarian structure [ovarian micro-organs (MOs)] induce angiogenesis and remained viable after autologous transplantation in animals. We report that preparation of autologous tiny ovarian fragments (MO)s and reimplantation into our patient resulted in IVF pregnancy and delivery of a healthy baby.

Repeated implantation failure: clinical approach

Successful embryo implantation depends on a well-functioning endometrium as well as a normal healthy embryo. This process might be hampered if either of these variables is defective. Repeated implantation failure (RIF) is diagnosed when good-quality embryos repeatedly fail to implant after transfer in several IVF treatment cycles. The causes of RIF originate with either the mother or the embryo. The authors discuss factors that are associated with RIF and address various treatment options.

Male Hyperprolactinemia: Effects on Fertility *

Male hyperprolactinemia was detected in 4% (7 of 171) of infertile men. In seven patients with excessive serum prolactin concentrations, the clinical manifestations were infertility, hypogonadism, impotence, and galactorrhea and the etiologic factors were pituitary adenoma, hypothalamic dysfunction, drug use, and idiopathic. The testes and prostate were small or normal and the semen analysis revealed low semen volume, normal or low sperm count, and normal or impaired sperm motility. The testicular biopsy showed normally preserved seminiferous tubules with normal or decreased spermatogenesis and damaged or fibrotic seminiferous tubules among normal ones. Patients with hyperprolactinemia were investigated by sellar polytomography, visual field examinations, and hormone assays. Treatment with bromocriptine (Parlodel) gave satisfactory results in all patients. The use of bromocriptine with human menopausal gonadotropin and human chorionic gonadotropin was beneficial in treating hypogonadotropic hypogonadism with hyperprolactinemia.

Evaluation and Treatment of Low Responders in Assisted Reproductive Technology: A Challenge to Meet

Purpose: To investigate the various methods of evaluationand treatment of patients with a low response to controlledovarian hyperstimulation in assisted reproductive technologies (ART). Methods: Review and analysis of relevant studies publishedin the last decade, identified through the literature and Medlinesearches. Results: While a universally accepted definition for lowresponders is still lacking, these patients are reported torepresent about 10% of the ART population. Several ovarianreserve screening techniques have been proposed; however,currently the best-characterized and most sensitive screeningtools available are the basal day 3 serum follicle-stimulatinghormone level and the clomiphene citrate challenge test.When abnormal, these tests allow physicians to counselpatients that their prognosis for conception is poor. Althoughthe presence of a normal result does indicate better long-termchances for conception, an age-related decline in fecundityremains and patient age should still be considered whencounseling patients with normal screening results. Severalstimulation protocols have been applied in the low-responsegroup with varying success. Recent studies show that theuse of a minidose gonadotropin-releasing hormone-agonistprotocol may result in significantly decreased cycle cancellationsas well as increased clinical and ongoing pregnancies,and thus is proposed as a first-line therapy. Studies evaluatingsupplementary forms of treatment to the ovulation inductionregimen show improved outcome when pretreating withoral contraceptives, whereas there seems to be no benefitfrom cotreatment with growth hormone or glucocorticoids.Blastocyst culture and transfer and assisted hatching in lowresponders are still under evaluation, whereas natural cyclein vitro fertilization may be used in cases of repeated failuresas a last option before resorting to oocyte donation or adoption.Future possible forms of treatment like in vitro maturationof immature human oocytes, cytoplasm, and nucleartransfer currently are experimental in nature and their efficacyhas still to be proven.Conclusions: The evaluation and treatment of low respondersin ART remains a challenge. Understanding of the underlyingetiology and pathophysiology of this disorder may helpthe clinician to approach it successfully.

Assessment and treatment of repeated implantation failure (RIF).

Repeated implantation failure (RIF) is determined when embryos of good quality fail to implant following several in vitro fertilization (IVF) treatment cycles. Implantation failure is related to either maternal factors or embryonic causes. Maternal factors include uterine anatomic abnormalities, thrombophilia, non-receptive endometrium and immunological factors. Failure of implantation due to embryonic causes is associated with either genetic abnormalities or other factors intrinsic to the embryo that impair its ability to develop in utero, to hatch and to implant. New methods of time-lapse imaging of embryos and assessment of their metabolic functions may improve selection of embryos for transfer, and subsequent outcomes for IVF patients, as well as for those diagnosed with RIF. This review discusses the various causes associated with RIF and addresses appropriate treatments.

Gonadotropin-Releasing Hormone (GnRH)-Antagonist Versus GnRH-Agonist in Ovarian Stimulation of Poor Responders Undergoing IVF

AbstractPurpose: The objective of this study was to compare the efficacy of GnRH-antagonists to GnRH-agonists in ovarian stimulation of poor responders undergoing IVF.nMethods: Retrospective analysis of our data revealed that 56 patients underwent treatment with a GnRH-agonist according to the flare-up protocol. Patients failing to achieve an ongoing pregnancy (n=53) were subsequently treated in the next cycle with a GnRH-antagonist according to the multiple-dose protocol. Main outcome measures included the clinical pregnancy and implantation rates.nResults: While ovulation induction characteristics and results did not differ between the two protocols, the number of embryos transferred was significantly higher (P=0.046) in the GnRH-antagonist than in the GnRH-agonist stimulation protocol (2.5 ± 1.6 vs. 2.0 ± 1.4, respectively). The clinical pregnancy and implantation rates per transfer in the GnRH-antagonist group appeared higher than in the GnRH-agonist, but did not differ statistically (26.1 and 10.7 compared with 12.2 and 5.9%, respectively). However, the ongoing pregnancy rate per transfer was statistically significantly higher (P=0.03) in the GnRH-antagonist than in the GnRH-agonist group (23.9 vs. 7.3%, respectively).nConclusion: Applying GnRH-antagonists to ovarian stimulation protocols may offer new hope for IVF poor responder patients. However, further controlled randomized prospective studies with larger sample sizes are required to establish these results.

Ovulation induction with clomiphene citrate complicated by deep vein thrombosis

A case of recurrent deep vein thrombosis following standard clomiphene citrate treatment, in a patient with a history of a previous episode of deep vein thrombosis, is described. This case indicates that deep vein thrombosis might be a rare but hazardous complication of clomiphene citrate treatment in patients with certain risk factors. We recommend that the use of clomiphene citrate in such cases be undertaken with caution and under close surveillance.

Novel parameters of human sperm hypoosmotic swelling test and their correlation to standard spermatogram, total motile sperm fraction, and sperm penetration assay.

OBJECTIVEnTo improve the accuracy of human sperm hypoosmotic swelling test by introducing new morphological evaluation parameters for this test.nnnDESIGNnIndividual semen samples were processed, and the standard spermatogram, total motile sperm fraction, sperm penetration assay (SPA), and hypoosmotic swelling test were performed.nnnSETTINGnMale infertility clinic and andrologic laboratory in a university medical center.nnnPATIENTSnOne hundred eighteen subfertile men undergoing an infertility work-up.nnnMAIN OUTCOME MEASURESnThe results of hypoosmotic swelling test were subdivided into four groups (hypoosmotic swelling test 1, 2, 3, 4) according to the different shapes of hypoosmotically affected spermatozoa tails.nnnRESULTSnThe hypoosmotic swelling test 3 had the best correlation with the different sperm parameters: motility, total motile sperm fraction, concentration, and SPA. The hypoosmotic swelling test 1 showed a satisfactory interrelation for concentration and for total motile sperm fraction but no correlation for motility and SPA. The hypoosmotic swelling test 2 and the hypoosmotic swelling test 4 demonstrated no correlation at all with motility, concentration, morphology and SPA.nnnCONCLUSIONSnThe precision of hypoosmotic swelling test may be improved by using the hypoosmotic swelling test 3 type of spermatozoa tail shape as the parameter for a normally functioning spermatozoa.

Menotropins as a possible risk factor for premature deliveries in triplet pregnancies

This study was undertaken in order to evaluate pregnancy outcome in three groups of triplet conceptions. Of 36 delivered triplet gestations, seven were spontaneous, 12 achieved using clomiphene citrate and 17 induced by menotropins. The mean gestational age (weeks) at delivery was 36.5 +/- 1.0 SD, for spontaneous and clomiphene citrate pregnancies it was 35.9 +/- 1.9 SD which differed significantly from that in pregnancies induced by menotropins which was 32.9 +/- 3.7 SD. Similarly, triplets born following menotropin treatment had a significantly lower gestational weight (g) of 1656 +/- 516 SD vs. 2015 +/- 198 SD and 2176 +/- 315 SD for spontaneous and clomiphene citrate gestations, respectively. It is concluded that triplets following menotropins are at an increased risk for premature delivery and low birth weight.

The value of an electronic microcomputerized basal body temperature measurement device (Bioself) in in vitro fertilization cycles

The Bioself 110 electronic basal body temperature (BBT) measurement device was employed in 18 women undergoing in vitro fertilization (IVF). This microcomputer-operated device records, charts and accurately analyzes the mean temperature measurements. These temperature recordings were used in addition to transvaginal ovarian sonography and serum estradiol and progesterone levels. The BBT rise correlated significantly (p < 0.0002) with progesterone elevation following human chorionic gonadotropin (hCG) administration. It is suggested that this electronic device may be used as an additional tool in the detection of premature progesterone secretion in IVF cycles.