Objective: In general, patients with low ovarian reserve nosis. Using traditional stimulation protocols like the long GnRH agonist protocol or the GnRH antagonist protocol in these patients often results in low ovarian response and poor pregnancy rates. In natural menstrual cycles without ovarian stimulation, every month the female body naturally selects the best possible oocyte for ovulation. nevertheculties to conceive naturally. We observed the menstrual cycle pattern of patients with low ovarian reserve in order we were able to describe the different stages, we developed new treatment approaches for each patient group based on natural Cycle IVF. Methods: In 2012, the menstrual cycle pattern of 10 patients with AMH <1.0 nmol/L were observed. Patients were 22 – 42 years old (average 39.3). Blood samples were drawn to determine AMH, FSH, LH, E2 and transvaginal ultrasound scans were performed on different days of the cycle. Depending on the cycle pattern of each patient, we offered individualized treatment approaches based on natural Cycle IVF using Clomifen citrate to control ovulation, GnRH agonists to induce ovulation and either Ethinyl-Estradiol or combined oral contraceptive pills to regulate the cycle. Embryos cial cycles. Patients were informed about off label use of the medication and informed consents were signed. Results: Based on our observation, we could describe four perform oocyte retrievals and embryo transfers in all 10 patients. A total of 33 natural cycles were initiated. Premature ovulation occurred in 3 cycles (9.0%) and no retrieval was attempted. Among the attempted 30 oocyte retrievals, 21 (70.0%) were successful. Out of those 21 oocytes 11 (36.6% per retrieval) were mature and 10 (33.3% per retrieval) were immature. ICSI resulted in 8 fertilizations (72.7% per mature oocyte). Out of 8 transfers, 3 (37.5%) resulted in biochemical pregnancy. Two patients delivered (25.0%), one patient had a miscarriage at 8 weeks of pregnancy. Conclusion: Our experience shows that ovulation can successfully be controlled by the use of Clomiphene citrate and does not necessarily require GnRH analogues for pituitary suppression. This knowledge opens new space for development of alternative protocols respecting the patients’ own physiology with no need for heavy stimulation. Patients with can be offered before referring them to egg donation. INTRODUCTION For the last 30 years, the so-called “long gonadotropin releasing hormone agonist (GnRHa) pituitary suppression regimen” with relatively high doses of exogenous follicle combined-stimulating hormone (FSH) remains the most frequently used stimulation protocol. The success of this protocol is mostly based on the fact that pituitary suppression and exogenous ovarian stimulation can be easily learand easy to schedule, which makes IVF practicable for clinics all over the world. A deeper understanding of each patient’s particular cycle pattern is not really necessary. Over the time the knowledge to observe the patient’s cycles and to learn from them, has been lost. Although the “long GnRHa pituitary suppression regimen” works very well in many patients, there are certain patient groups, which are tly to ovarian stimulation and their treatment cycles are often canceled. So far, the lack of deeper understanding of ovarian physiology has prevented the development of alternative treatment approaches for these patient groups. Yet another stimulation protocol for IVF, which has recently been described by Teramoto (Teramoto & Kato, 2007), involves the use of 50 mg Clomiphene citrate from cycle day 3 onwards. This new protocol is designated as “minimal ovarian stimulation”. It is not designed for women with low ovarian reserve in particular. Clomiphene is administered in this method for a relatively long period of time, i.e. 10-12 days until the day before maturation is triggered by administration of a GnRH agonist. Oocytes are then retrieved 32-35 h later. By this method Teramoto makes use of the antagonistic action of Clomiphene citrate to the estradiol receptor on the hypothalamus level, inhibiting both positive and negative feedback, and resulting in the induction of the ovarian stimulation and suppression of ovulation. patients, our group used the most empirical approach possible. We went back to pure observation of each patient’s cycle, trying to understand her individual hormorent types of ovulation. In a second step, we used an adapted treatment approach on each ovulation group. The different treatments were based on our personal experience and different approaches described in the literature, mainly those of Teramoto (Teramoto & Kato, 2007). natural Cycle IVF could successfully treat most patients. The only medication we used in these cases was Clomifen citrate (CC) to control ovulation. In other patients with ovulation disorders, we successfully applied Ethinyl-Estradiol (EE), combined oral contraceptive pills (COCP) or Clomiphene citrate depending on the pathology. The Original Article
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