briefly stated , in one aspect , the present invention describes a new pharmaceutical product containing a progesterone antagonist to be administered by the nasal route . in a preferred embodiment of the present invention the progesterone antagonist is intended to prevent the spontaneous mid cycle surge in coh treatments as part of art treatments . in another preferred embodiment of the present invention the progesterone antagonist contained in the new pharmaceutical product is mifepristone ( ru486 ). mifepristone is a competitive inhibitor of the progesterone receptor ( pr ), which is the basic mechanism of action underlying the already approved indication for the induction of the medical aborption . among other functions , prs are involved in a cyclic complex signalling between the ovary and the hypothalamus . the rising concentration of ovarian estradiol in the late follicular phase induces the exposure of prs in the hypothalamus . once progesterone comes available for binding , which occurs at the end of the follicular phase , the hypothalamus changes the pattern of release of its gnrh from pulsatile to massive . the surge of gnrh causes in turn a surge of gonadotrophins , especially of lh , from the pituitary . the above described event is known as ovulatory surge because under the stimulation of a huge amount of lh the oocyte of the leading ovarian follicle will resume the meiotic division and complete the maturation while the granulosa cells constituting the oocyte cumulus will loosen their junctions to finally liberate the mature oocyte into the tube . patients suffering from reproductive problems may need to undergo a controlled ovarian hyperstimulation ( coh ) cycle as par of an art program . in these cycles an early spontaneous gonadotrophin surge may cause an early release and loss of the oocytes , therefore it is necessary to keep the release of the surge under control . mifepristone , due to its pr competitive inhibition , has the potential to reversibly block the hypothalamic pr and thus to delay the occurrence of the gonadotrophin surge as long as needed for the success of the coh cycle . such use has been already proven in published clinical studies . however , the pr antagonism of mifepristone is also responsible for antifolliculogenetic effects and in clinical studies the dose causing perturbation of the folliculogenesis was very close if not overlapping the dose effective in the prevention of the gonadotropin surge . this problem makes the therapeutic window of mifepristone in this indication too narrow for a realistic clinical suitability . it has been now discovered that the rate of mifepristone bioavailable at the hypothalamic site can be increased at the expense of the rate reaching the circulation by administering mifepristone by the nasal route , which addresses the above outlined problem and constitutes the basic novelty of the present invention . the nasal route has the potential to deliver molecules directly to the brain , i . e . by nose to brain route , by means of both intracellular and intercellular transport pathways and has already resulted in successful selective cns delivery of drugs . mifepristone , thanks to its high lipid solubility , is particularly suitable for nose to brain delivery , as already demonstrated for similarly lipid soluble steroids , i . e . estrogen and progesterone . the present invention is therefore represented by a pharmaceutical product containing an antiprogestinic molecule for use in the temporary suppression of the spontaneous midcycle gonadotrophin surge in women undergoing follicular stimulation for assisted reproduction ( art ) purposes by delivery of the antiprogestinic molecule to the cns . more specifically , the present invention is represented by a pharmaceutical product containing an antiprogestinic molecule for use in the temporary suppression of the spontaneous midcycle gonadotrophin surge in women undergoing follicular stimulation for assisted reproduction ( art ) purposes by nasal administration , i . e . nose to brain delivery . in a preferred embodiment of the present invention mifepristone is formulated for nasal administration as a liquid solution in organic solvents including , but not limited to , ethanol and dimethyl sulfoxide ( dmso ), both capable to dissolve more than 20 mg / ml of mifepristone . in alternative , mifepristone is formulated as a solution in organic oil . even though preferentially delivered to the cns , mifepristone may keep some antifolliculogenetic potential , thus it is necessary to limit its administration only to the days of the coh cycle that are at real risk of early occurrence of the gonadotrophin surge . such risk became real when the first leading follicle within the stimulated cohort reaches maturity because it will start releasing small amounts of progesterone that may be however enough to trigger a system already strongly primed by high estrogens . such level of maturity is certainly not reached until the follicle has a diameter of 16 mm and it is from this time that mifepristone nasal administration should start . however , in the sake of full follicular safety and if precise ultrasonografic measurement is available , it may be advisable to slightly delay the start of mifepristone dosing up to the time follicles reach sizes of 20 mm . in a preferred embodiment of the present invention mifepristone nasal delivery starts when the leading follicle reach the diameter of 16 mm , preferably 18 mm , more preferably 20 mm . in any case , mifepristone dosing should not start later than day 8 of fsh administration within coh cycles . once administered by the nasal , i . e . nose to brain , route , only a small part of the total dose , but likely more than the 2 % supposed to be delivered to the cns by an oral administration , will be bioavailable at the hypothalamic compartment by a direct nose to brain pathway . however , the ic 50 for mifepristone - induced competitive binding to pr wild type receptor is as low as 0 . 1 nm 24 . thus , assumed the small volume of distribution of the cns , roughly one liter , the actual absorption and transport into the cns of just 50 nanograms of mifepristone , equal to 0 . 005 % of a 1 mg nasal dose , is enough to reach the threshold of prs inhibition . accordingly , the administered dose may be as well low to minimise the exposure of extra - cns districts . in a preferred embodiment of the present invention mifepristone is administered at a daily nasal dose of 0 . 1 - 10 mg , preferably 0 . 5 - 5 mg , more preferably 0 . 75 - 2 . 5 mg . once started , mifepristone nasal administration should continue in parallel with fsh administration until the targeted development of the follicles is reached , i . e . when a good number of follicles appear to be ready for the final maturation . in practice , the day of fsh withdrawal will also be the day of mifepristone withdrawal . thereafter , the gonadotrophin surge will occur either spontaneously or following triggering with natural progesterone . in a preferred embodiment of the present invention , once mifepristone is withdrawn , the gonadotrophin surge occurs spontaneously within 2 to 3 days . in another preferred embodiment of the present invention , once mifepristone is withdrawn , the gonadorophin surge is stimulated by the administration of natural progesterone . in a complementary aspect the present invention also provides a new method to perform a coh cycle that is based on the availability of mifepristone for nasal delivery . briefly , the cycle is started with the administration of the daily dose of fsh that is normally selected for that type of patient and is thereafter titrated according to the ovarian response as usually done . it is noted that no pituitary suppression regimen is established and that no lh supplementation is required as the pituitary will release lh as and when needed to balance the fsh activity . when the leading follicles reach the diameter of 16 - 18 mm , nasal mifepristone at very low doses is started in parallel with continuing fsh administration . once the targeted development is reached , i . e . a good number of follicles are ready to ovulate , both fsh and mifepristone are discontinued . the administration of nasal progesterone starts on the first day of fsh / mifepristone withdrawal and continues for 48 hours while plasma lh is monitored to detect the initial rise of the surge . the oocytes pick - up is planned at 48 hours from the start of lh rise . thereafter the oocytes are fertilised and the embryos transferred according to the usual practices . the embryo transfer does not need to be sustained with a luteal support treatment . the new method is innovative with respect to the state of the art in a series of aspects as follows : 1 . differently from the state of the art , the cycle is not started with a pituitary desensitisation treatment , neither it will include any gnrh antagonist later on . besides saving resources , the avoidance of the pituitary suppression allows a stimulation cycle under pituitary control . indeed , in these conditions the pituitary is expected to account for any changes of the endocrine milieu so to create the best conditions for the follicles growth . 2 . as a consequence of 1 , in the majority of patients there will be no need to include a lh supplementation in parallel to fsh administration . indeed , the pituitary will be able to release lh pulses with the appropriate frequency , amplitude and lh isoform composition . again , this is a saving in resources but also an increase of the quality of the stimulation because exogenous lh agonists administered under pituitary blockade , besides in part substituting the lacking hormone , also further interfere the feedbacks reaching the pituitary misleading also the minimal residual pituitary secretion . 3 . differently from the state of the art , the ovulatory gonadotropin surge will be natural , i . e . released by the pituitary , either spontaneously occurring after nasal mifepristone discontinuation or triggered by administration of natural progesterone . 4 . differently from the state of the art , in the majority of patients the embryo transfer will not require to be sustained with a luteal support . indeed , the active pituitary regulation balancing the background endocrine milieu will also benefit the endometrium accounting for the disturbances generated by the supraphisiological fsh amounts and the supraphysiological estrogen levels . as regards the use of natural progesterone for triggering the gonadotropin surge , it is to be noted that this will benefit the coh cycle in two different ways . first , as largely explained herein , progesterone will activate the pr of the hypothalamus so far inhibited by mifepristone . indeed , the inhibition is competitive , i . e . it is directly related to the relative concentration of progesterone and of its antagonist . following discontinuation of mifepristone , its cns concentration will start to decline while progesterone concentration rise under active dosing , which will cause a fast inversion of the receptors occupancy . the rapidity of such conversion will be directly proportional to the amount of progesterone delivered , i . e . to the amount and to the frequency of progesterone dosing . on the other side , it will be inversely correlated to the amount of mifepristone previously administered . second , in the physiologic cycle the lh surge acts by stimulating both granulosa cell progesterone production and granulosa exposure of prs . in these conditions progesterone acts via genomic mechanisms involving nuclear progesterone receptors and non - genomic mechanisms by the activation of a putative membrane pr . a main effect of such follicular progesterone activation will be the loosening of the gap junctions of the oocyte cumulus that start the events leading to the release of the oocyte . inasmuch , dosing progesterone to trigger the gonadotrophin surge will also start the events caused by the same surge and will be synergic with the effect of the surge on the final maturation and release of the oocyte . as a consequence of the above arguments , the maximum dose of progesterone to be used to trigger the gonadotropin surge is not critical , i . e . it can be in excess on the minimal need , but it is critical to reach the minimal need at the cns compartment . moreover , aiming to well timed gonadotropin surge , it is important that threshold concentration of progesterone is reached at the hypothalamic level within a short time following fsh withdrawal with a sort of peak effect . this can be obtained by the intranasal delivery of progesterone , possibly at relatively high amounts by repeated doses at short intervals . on the other side , the excess of progesterone delivered as such and entering the bloodstream is not a problem , rather it benefits the effects of the gonadotropin surge occurring thereafter by somehow anticipating the effect on the cumulus cells that the lh peak is known to have . in a preferred embodiment of the present invention the new method for coh includes triggering of the gonadotrophins surge by delivery of progesterone to the cns , preferably by the nasal route . in another preferred embodiment of the present invention the new method for coh include administration of nasal progesterone starting from the first day of fsh and mifepristone withdrawal . in another preferred embodiment of the present invention the new method for coh include administration of nasal progesterone at doses in excess to the minimal need to remove the mifepristone blockade and with repeated administrations in short distance such as 1 - 20 mg , preferably 2 - 10 mg , and at intervals of 8 hours , preferably 4 hours , more preferably 2 hours up to the confirmed occurrence of the gonadotrophin surge . the occurrence of the gonadotrophin surge is confirmed by monitoring the plasma concentration of lh . the actual persistence of very high circulating lh in case of a natural cycle is in the range of 48 hours . accordingly , aiming to sustain the surge over time , progesterone dosing will be changed as soon as there will be clear evidence of progressive rise of lh . starting from this point progesterone will be administered at fixed 8 hours intervals up to completion of an overall progesterone treatment of 48 hours . the follicular events following the occurrence of the surge take approximately 48 hours to complete , therefore the oocytes will be ready for the pick - up 48 hours later than the confirmed occurrence of the lh surge , i . e . within 72 hours from the first progesterone dose . in alternative , the lh peak may be obtained without any further treatment , i . e . waiting for a longer time , likely 3 days , after fsh and mifepristone discontinuation and the oocyte pick - up is planned 48 hours following confirmed start of the surge . as a further alternative , a progesterone bolus and a hcg bolus are administered at time of fsh and mifepristone discontinuation and the oocyte pick - up is planned at 72 hours post - dosing . the new pharmaceutical product described in the present invention , i . e . a progesterone antagonist such as mifepristone ( ru486 ) formulated for intranasal ( i . e . nose to brain ) delivery , is easily suitable for manufacturing at industrial scale because : i ) the active pharmaceutical ingredient is largely available in the market and not protected by active intellectual properties ; ii ) the formulation for intra - nasal administration can be achieved without recurring to difficult or expensive ingredients ; iii ) the technologies for manufacturing as a liquid formulation , scaling - up at industrial sizes and primary and secondary packaging suitable for nasal delivery are widely available in the state of the art ; iv ) the potential market demand , in the range of millions of daily doses per year , is compatible with the industrial economy scale . patients referring to a specialised human reproduction centre due to idiopathic infertility are administered fsh from day 2 of the follicular cycle at starting daily doses equal to 150 iu for patients with a body mass index ( bmi ) & lt ; 25 and equal to 225 iu in patients with a bmi & gt ; 25 or carrying known resistance factors . no pituitary suppression is established neither a lh containing drug is associated to fsh . the cycle is monitored by transvaginal ultrasonographic scan ( tv - us ) starting from day 5 of stimulation and thereafter any other day and the dose of fsh is titrated according to the follicle growth . when at least 2 follicles reach the diameter of 16 mm mifepristone administration starts . mifepristone is given at 1 mg daily doses by the nasal route while fsh administration continues at the doses suggested by the follicles response . at the first planned monitoring session in which the tv - us reveals at least 1 follicle having a diameter of 20 mm , fsh and mifepristone are discontinued and progesterone dosing starts on the same day . progesterone is given by the nasal route at doses of 5 mg at 4 hours intervals for 20 hours ( 5 doses ) and lh circulating level is checked at 24 hours ( 4 hours after the last progesterone dose ): the lh peak is assumed as triggered for any value of circulating lh higher than 30 iu per litre . patients whose lh is higher than such cut - off value undergo further administration of 5 mg intranasal progesterone at 8 hours intervals for another 24 hours . patients below the lh cut - off value continue progesterone dosing at 4 hours intervals until the targeted lh cut - off value is reached , thereafter they complete the cycle with dosing at 8 hours intervals as previously described . the oocyte pick - up is planned at 24 hours after the last progesterone dose . the fsh stimulation and the mifepristone nasal dosing as well as the monitoring procedure are performed as described in example 1 and these drugs are discontinued according to the same criteria . at the first planned monitoring session in which the tv - us reveals at least 1 follicle having a diameter of 18 mm , mifepristone is discontinued whereas fsh dosing continues for another day and then is discontinued as well . plasma lh levels are monitored at 12 hours interval starting from 24 hours following fsh discontinuation . the oocyte pick - up is planned at 48 hours following the first rise of plasma lh higher than 30 iu per litre . the fsh stimulation and the mifepristone nasal dosing as well as the monitoring procedure is performed as described in example 1 . thereafter , at the first planned monitoring session in which the tv - us scan reveals at least 1 follicle having a diameter of 20 mm , fsh and mifepristone are discontinued and the lh surge is triggered with a bolus of 25 mg progesterone , either intranasal or injectable , and 5 ′ 000 iu of hcg . the oocyte pick - up is planned 72 hours later . 1 . arslan , m et al .— controlled ovarian hyperstimulation protocols for in vitro fertilization : two decades of experience after the birth of elizabeth carr . fertil . steril . 2005 ; 84 ( 3 ): 555 - 69 . 2 . hayden , c — gnrh analogues : applications in assisted reproductive techniques . eur . j . endocrinol . 2008 ; 159 ( suppl 1 ): s17 - s25 . 3 . humaiden , p et al .— gnrha to trigger final oocyte maturation : a time to reconsider . hum reprod . 2009 ; 24 ( 10 ): 2389 - 2394 . 4 . micevych , p & amp ; sinchak k — estradiol regulation of progesterone synthesis in the brain . mol . cell endocrinol . 2008 ; august 13 ; 290 ( 1 - 2 ): 44 - 50 . 5 . cadepond , f et al .— ru486 ( mifepristone ): mechanisms of action and clinical uses . annu . reev . med . 1997 ; 48 : 129 - 156 . 6 . permezel , j m et al .— acute effects of progesterone and the antiprogestin ru486 on gonadotropin secretion in the follicular phase of the menstrual cycle . j . clin . endocrinol . met . 1989 ; 68 ( 5 ): 960 - 965 . 7 . batista , m c et al .— evidence for a critical role of progesterone in the regulation of the midcycle gonadotropin surge and ovulation . j . clin . endocrinol . met . 1992 ; 74 ( 3 ): 565 - 570 . 8 . croxatto h b et al .— follicle stimulating hormone - granulosa cell axis involvement in the antifolliculotrophic effect of low dose mifepristone ( ru486 ). human reprod . 1995 ; 10 ( 8 ): 1987 - 1991 . 9 . coelingh bennink , h j t & amp ; bunschoten , e j — ep1455831 - method of controlled ovarian hyperstimulation and pharmaceutical kit for use in such method . 10 . andersen , a n et al .— clinical outcome following stimulation with highly purified hmg or recombinant fsh in patients undergoing ivf : a randomized assessor - blind controlled trial . hum . reprod . 2006 ; 21 ( 12 ): 3217 - 3227 . 11 . pardridge , w m — the blood - brain barrier : the bottleneck in brain drug development . neurorx 2005 ; 2 : 3 - 14 . 12 . ill , l — transport of drugs from the nasal cavity to the central nervous system . eur . j . pharm . sci . 2000 ; 11 : 1 - 18 . 13 . thorne , r g — delivery of insulin - like growth factor - 1 to the rat brain and spinal cord along trigeminal pathway following intranasal administration . neuroscience 2004 ; 127 : 481 - 496 . 14 . reger , m a et al .— effect of intranasal insulin on cognition in memory impaired older adults : modulation by apoe genotype . neurobiol . aging 2006 ; 27 : 451 - 458 . 15 . yu , i p et al .— intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia . neurosci . letter 2005 ; 387 : 5 - 10 . 16 . jin , k et al .— cerebral neurogenesis is induced by intranasal administration of growth factors . annal . neurol . 2003 ; 53 : 405 - 409 . 17 . ying , w et al .— intranasal administration with nad + profoundly decreases brain injury in a rat model of transient focal ischemia . front . biosci . 2007 ; 12 : 2728 - 2734 . 18 . ying , w et al .— therapeutic potential of nad + for treating neurological diseases . future neurol . 2007 ; 2 : 129 - 132 . 19 . romano lagunas , g l et al .— effectiveness of nasal vs oral estrogens in the climacteric syndrome ( article in spanish ). gynecol obstet . mex . 2007 ; 75 ( 3 ): 127 - 32 . 20 . cicinelli , e et al .— administration of unmodified progesterone by nasal spray in fertile women . gynecol . endocrinol . 1995 ; 9 ( 4 ): 289 - 293 . 21 . escudero , e l et al .— mifepristone is an effective oral alternative for the prevention of premature luteinizing hormone surges and / or premature luteinization in women undergoing controlled ovarian hyperstimulation for in vitro fertilization . j . clin . endocrinl . metab . 2005 ; 90 ( 4 ): 2081 - 2088 . 22 . ulmann a . et al .— us 2010 / 261693 - a method for treating cushing syndrome . 23 . hausknecht r .— us 2007 / 213306 - methods , dosing regimens and medications using anti progestational agents for the treatment of disorders 24 . delabre , 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the present invention relates to a new pharmaceutical product containing an antiprogestin molecule , such as mifepristone , administered by the nasal route and to be used to modulate the timing of the spontaneous lh surge as part of follicular stimulation cycles intended for assisted reproductive technology . in particular , it details the route of administration and the dosages that ensure effective delay of the lh surge without incurring in the antifolliculogenetic effects of the antiprogestinic . it also details the overall treatment method as resulting from the use of the new drug product .