Response prediction Response predictors determine the protocol for ovulation suppression as well as dosage of medication used for<unk> . Response prediction based on<unk>  reserve confers substantially higher live birth rates, lower total costs and more safety. It is commonly agreed not to exclude anyone from their first IVF attempt only on the basis of poor results on response predictors, as the accuracy of these tests can be poor for the prediction of pregnancy. Antral follicle count The response to gonadotropins may be roughly approximated by antral follicle count (AFC), estimated by vaginal ultrasound, which in turn reflects how many primordial follicles there are in reserve in the ovary. The definition of "poor<unk>  response" is the retrieval of less than 4 oocytes following a standard<unk>  protocol, that is, following maximal stimulation. On the other hand, the term "hyper response" refers to the retrieval of more than 15 or 20 oocytes following a standard<unk>  protocol. The cut-offs used to predict poor responders versus normal versus hyper-responders upon vaginal ultrasonography vary in the literature, with that of likely poor response varying between an AFC under 3 and under 12, largely resulting from various definitions of the size follicles to be called antral ones. The following table defines antral follicles as those about 2–8 mm in diameter: Antral follicle count Classification Approximate expected response Risks Pregnancy rates Recommendation Less than 4 Extremely low Very poor or none Cancelled cycle expected 0–7% with 1 oocyte Not attempt IVF 4-7 Low Possibly/probably poor response Higher than average rate of IVF cycle cancellation 15% High doses of gonadotropin likely 8-10 Reduced Lower than average Higher than average rate of IVF cycle cancellation Slightly reduced 11-14 Normal (but intermediate) Sometimes low, but usually adequate Slight increased risk for IVF cycle cancellation Slightly reduced compared to the "best" group 15-30 Normal (good) Excellent Very low risk for IVF cycle cancellation. Some risk for<unk>  overstimulation Best overall as a group with approx. 35% Low doses of gonadotropins More than 30 High Likely high Overstimulation and<unk><unk>  syndrome Very good overall as a group, but potential egg quality issues Low doses of gonadotropins The incidence of poor<unk>  response in IVF ranges from 10 to 20%. Older poor responders have a lower range of pregnancy rates compared with younger ones (1.5–12.7 versus 13.0–35%, respectively). Also, the other way around, there is a lower prevalence of poor responders among young women compared to those of advancing age, with 50% of women aged 43– 44 years being poor responders. Other response predictors *Circulating anti-Müllerian hormone (AMH) can predict excessive and poor response to<unk>  stimulation. According to NICE guidelines of in vitro fertilization, an anti-Müllerian hormone level of less than or equal to 5.4 pmol/l (0.8 ng/mL) predicts a low response to<unk><unk> , while a level greater than or equal to 25.0 pmol/l (3.6 ng/mL) predicts a high response. For predicting an excessive response, AMH has a sensitivity and specificity of 82% and 76%, respectively. Overall it may be superior to AFC and basal FSH. Tailoring the dosage of gonadotrophin administration to AMH level has been shown to reduce the incidence of excessive response and cancelled cycles. *Elevated basal Follicle stimulating hormone (FSH) levels imply a need of more ampoules of gonadotropins for stimulation, and have a higher cancellation rate because of poor response. However, one study came to the result that this method by itself is worse than only AMH by itself, with live birth rate with AMH being 24%, compared with 18% with FSH. *Advanced maternal age causes decreased success rates in<unk><unk> . In<unk><unk>  combined with IUI, women aged 38–39 years appear to have reasonable success during the first two cycles, with an overall live birth rate of 6.1% per cycle. However, for women aged ≥40 years, the overall live birth rate is 2.0% per cycle, and there appears to be no benefit after a single cycle of<unk> /IUI. It is therefore recommended to consider in vitro fertilization after one failed<unk> /IUI cycle for women aged ≥40 years. *Body mass index *Previous<unk>  experiences *Length of menstrual cycles, with shorter cycles being associated with poorer response. *Previous<unk>  surgery.<unk>  medications FSH preparations Nomogram for the starting dosage of FSH preparation as estimated from age, antral follicle count (AFC) and endogenous serum FSH taken day 3 of the menstrual cycle. An example is given in the nomogram, wherein an age of 32 years and an AFC of 12 gives a point on the middle line that, when continued to an FSH of 5 IU/l, results in a starting FSH dosage of almost 200 IU/l. Nomogram for the starting dosage of FSH as estimated from age, anti-Müllerian hormone (AMH) and endogenous serum FSH taken day 3 of the menstrual cycle (same as previous nomogram but with AMH instead of AFC). In most patients injectable gonadotropin preparations are used, usually FSH preparations. The clinical choice of gonadotrophin should depend on availability, convenience and costs. The optimal dosage is mainly a trade-off between the pregnancy rate and risk of<unk><unk>  syndrome. A meta-analysis came to the result that the optimal daily recombinant FSH stimulation dose is 150 IU/day in presumed normal responders younger than 39 years undergoing IVF. Compared with higher doses, this dose is associated with a slightly lower oocyte yield, but similar pregnancy rates and embryo cryopreservation rates. For women predicted to have a poor response, there may not be any benefit to start at a higher FSH dosage than 150 IU per day. When used in medium dosage, a long-acting FSH preparation has the same outcome in regard to live birth rate and risk of<unk><unk>  syndrome as compared to daily FSH. A long-acting FSH preparation may cause decreased live birth rates compared to daily FSH when using low dosages (60 to 120 µg of corifollitropin alfa). Recombinant FSH (rFSH) appears to be equally effective in terms of live birth rate compared to any of the other types of gonadotropin preparations irrespective of the protocol used for ovulation suppression. Typically approximately 8–12 days of injections are necessary. Alternatives and complements to FSH Administering recombinant hCG in addition to an FSH-preparation has no significant beneficial effect. Clomifene in addition to gonadotropins may make little or no difference to the live birth rate but may lower the probability of<unk><unk>  syndrome. A systematic review showed that using clomifene citrate in addition to low dose gonadotropin (in a GnRH antagonist protocol as described in the following section) resulted in a trend towards better pregnancy rates and a greater number of oocytes retrieved when compared with a standard high-dose FSH regime. Such a protocol avails for using lower dosages of FSH-preparations, conferring lower costs per cycle, being particularly useful in cases where cost is a major limiting factor. Recombinant luteinizing hormone (rLH) in addition to FSH probably increases pregnancy rates, but it is not certain if the live birth rate is also increased. Using low dose human chorionic gonadotropin (hCG) to replace FSH during the late follicular phase in women undergoing<unk>  as part of IVF may make little or no difference to pregnancy rates, and possibly leads to in an equivalent number of oocytes retrieved, but with less expenditure of FSH. Before<unk>  stimulation with antagonist protocols, pretreatment with combined oral contraceptive pills probably reduces the rate of live birth or ongoing pregnancy, while it is uncertain whether pretreatment with progesterone only has any effect on live birth or ongoing pregnancy rates. For other stimulation protocols, the evidence around pretreatment with combined oral contraceptives and progesterone only is uncertain. Findings are conflicting, but metformin treatment as a complement in IVF cycles may reduce the risk of<unk><unk>  syndrome and increase live birth rates. Suppression of spontaneous ovulation When used in conjunction with in vitro fertilization (IVF),<unk>  confers a need to avoid spontaneous ovulation, since oocyte retrieval of the mature egg from the fallopian tube or uterus is much harder than from the<unk>  follicle. The main regimens to achieve ovulation suppression are: *GnRH agonist administration given continuously before starting the gonadotropin<unk>  regimen. Physiologically, GnRH agonists are normally released in a cyclical fashion in the body to increase normal gonadotropin release, including luteinizing hormone that triggers ovulation, but continuous exogenous administration of GnRH agonists has the opposite effect of causing cessation of physiological gonadotropin production in the body. *GnRH antagonist administration, which is typically administered in the mid-follicular phase in stimulated cycles after administration of gonadotropins and prior to triggering final maturation of oocytes. The GnRH antagonists that are currently licensed for use in fertility treatment are cetrorelix and ganirelix. In GnRH antagonist cycles,<unk>  medication is typically started on the second or third day of a previous natural menstruation. Agonist vs antagonist Regarding pregnancy rate, choosing GnRH agonist protocol for a cycle is approximately as efficient as choosing GnRH antagonist protocol. Still, the two protocols differ on a number of aspects: *Practically, the timing of the
Controlled ovarian hyperstimulation
Ovarian stimulation
Postpartum confinement
Menstrual extraction
Vasectomy reversal
Oxytocin
Oxytocin 
Anovulatory cycle